Difference between revisions of "HAEM5:Childhood myelodysplastic neoplasm with low blasts"

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(Created page with "{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with low blasts}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote class='b...")
 
 
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{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with low blasts}}
 
{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with low blasts}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
  
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Refractory Cytopenia of Childhood]].
+
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Refractory Cytopenia of Childhood]].
 
}}</blockquote>
 
}}</blockquote>
 +
 +
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>
 +
 
==Primary Author(s)*==
 
==Primary Author(s)*==
  
Line 11: Line 14:
  
 
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
 
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
 +
==WHO Classification of Disease==
  
__TOC__
 
 
==Cancer Category/Type==
 
 
Myelodysplastic Syndrome
 
 
==Cancer Sub-Classification / Subtype==
 
 
Refractory Cytopenia of Childhood
 
 
==Definition / Description of Disease==
 
 
Refractory Cytopenia of Childhood (RCC) is a low-grade MDS most common in childhood, which is characterized by <2% blood blasts and <5% bone marrow blasts and persistent cytopenia<ref>{{Cite journal|last=Hasle|first=H.|last2=Niemeyer|first2=C. M.|last3=Chessells|first3=J. M.|last4=Baumann|first4=I.|last5=Bennett|first5=J. M.|last6=Kerndrup|first6=G.|last7=Head|first7=D. R.|date=2003-02|title=A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases|url=https://pubmed.ncbi.nlm.nih.gov/12592323|journal=Leukemia|volume=17|issue=2|pages=277–282|doi=10.1038/sj.leu.2402765|issn=0887-6924|pmid=12592323}}</ref>. Since more than 80% RCC has a hypocellular bone marrow, it is important to distinguish RCC with aplastic anemia from other bone marrow failure disorders<ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref>. Aplastic anemia is an autoimmune-mediated disorder, while RCC is caused by a clonal stem cell defect with the potential to progress to an advanced disease. The presence of micromegakaryocytes is a strong indicator of RCC. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment<ref name=":0">Arber DA, et al., (2016). WHO Classification of Tumours    of Haematopoietic and Lymphoid Tissues, revised 4<sup>th</sup> edition. Swerdlow    SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors.    IARC Press: Lyon, France, p106-109.</ref>.  
 
 
==Synonyms / Terminology==
 
 
Refractory Cytopenia of Childhood (RCC)
 
 
==Epidemiology / Prevalence==
 
 
RCC accounts for 50% of all cases of MDS<ref name=":0" /> <ref>{{Cite journal|last=Passmore|first=S. Jane|last2=Chessells|first2=Judith M.|last3=Kempski|first3=Helena|last4=Hann|first4=Ian M.|last5=Brownbill|first5=Pat A.|last6=Stiller|first6=Charles A.|date=2003-06|title=Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival|url=https://pubmed.ncbi.nlm.nih.gov/12780790|journal=British Journal of Haematology|volume=121|issue=5|pages=758–767|doi=10.1046/j.1365-2141.2003.04361.x|issn=0007-1048|pmid=12780790}}</ref><ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Giagounidis|first3=Aristoteles|last4=Haas|first4=Rainer|last5=Gattermann|first5=Norbert|last6=Starke|first6=Carsten|last7=Aul|first7=Carlo|date=2012-06|title=Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/22421409|journal=Leukemia Research|volume=36|issue=6|pages=727–734|doi=10.1016/j.leukres.2012.02.014|issn=1873-5835|pmid=22421409}}</ref>.
 
 
*Most common childhood MDS
 
*No significant sex predilection
 
 
==Clinical Features==
 
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
 
{| class="wikitable"
 
{| class="wikitable"
|'''Signs and Symptoms'''
+
!Structure
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
!Disease
 
+
|-
EXAMPLE B-symptoms (weight loss, fever, night sweats)
+
|Book
 
+
|Haematolymphoid Tumours (5th ed.)
EXAMPLE Fatigue
+
|-
 
+
|Category
EXAMPLE Lymphadenopathy (uncommon)
+
|Myeloid proliferations and neoplasms
 +
|-
 +
|Family
 +
|Myelodysplastic neoplasms
 +
|-
 +
|Type
 +
|Myelodysplastic neoplasms of childhood
 
|-
 
|-
|'''Laboratory Findings'''
+
|Subtype(s)
|EXAMPLE Cytopenias
+
|Childhood myelodysplastic neoplasm with low blasts
 
 
EXAMPLE Lymphocytosis (low level)
 
 
|}
 
|}
  
 
+
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
+
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
 
 
The clinical symptoms are usually related to cytopenia such as anemia, bleeding tendency, and infection. However, approximately 20% of patients have no clinical symptoms or signs<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref>.
 
 
 
*Hemoglobin concentration: <10 g/dL AND
 
*Platelet count: <150 x10<sup>9</sup>/L
 
 
 
</blockquote>
 
==Sites of Involvement==
 
 
 
Peripheral blood and bone marrow
 
 
 
==Morphologic Features==
 
 
 
The main morphologic features of the peripheral blood smear and bone marrow are for the diagnosis of RCC<ref name=":0" />.
 
 
{| class="wikitable"
 
{| class="wikitable"
 
|+
 
|+
!'''Categories'''
+
|WHO Essential Criteria (Genetics)*
!'''Morphologic Features'''
+
|
 
|-
 
|-
|Peripheral blood
+
|WHO Desirable Criteria (Genetics)*
|Anisopoikilocytosis and macrocytosis; neutropenia with pseudo-Pelger-Huet nulei, hypogranularity or agranularity,
+
|
 +
|-
 +
|Other Classification
 +
|
 +
|}
 +
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
 +
==Related Terminology==
 +
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
 +
{| class="wikitable"
 +
|+
 +
|Acceptable
 +
|
 
|-
 
|-
|Bone marrow aspirate/biopsy
+
|Not Recommended
|Erythropoiesis: immature erythroid precursors, nuclear budding, multinuclearity, internuclear bridging;
+
|
 
 
Graulopoiesis: pseudo-Pelger-Huet nulei, hypogranularity or agranularity, macrocytic bands;
 
Megakaryopoiesis: absent or very few, however, micromegakaryocyte is crucial for the diagnosis.
 
 
|}
 
|}
  
==Immunophenotype==
+
==Gene Rearrangements==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
  
 +
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Finding!!Marker
+
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
 +
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
 +
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
 +
!Established Clinical Significance Per Guidelines - Yes or No (Source)
 +
!Clinical Relevance Details/Other Notes
 
|-
 
|-
|Positive (universal)||EXAMPLE CD1
+
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
 +
|<span class="blue-text">EXAMPLE:</span> Common (CML)
 +
|<span class="blue-text">EXAMPLE:</span> D, P, T
 +
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
 +
|<span class="blue-text">EXAMPLE:</span>
 +
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
 
|-
 
|-
|Positive (subset)||EXAMPLE CD2
+
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|-
+
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|Negative (universal)||EXAMPLE CD3
+
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
 +
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
 +
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
 +
|<span class="blue-text">EXAMPLE:</span> D
 +
|
 +
|<span class="blue-text">EXAMPLE:</span>
 +
 
 +
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
 
|-
 
|-
|Negative (subset)||EXAMPLE CD4
+
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|}
+
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
+
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
 
+
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
CD61, CD41, von Willebrand factor are useful to help detect the micromegakaryocyte. No increase of CD34 staining should be observed, which indicates the progression of high grade MDS<ref name=":0" />.
+
|<span class="blue-text">EXAMPLE:</span> N/A
 +
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
 +
|<span class="blue-text">EXAMPLE:</span> T
 +
|
 +
|<span class="blue-text">EXAMPLE:</span>
  
</blockquote>
+
Both balanced and unbalanced forms are observed by FISH (add references).
==Chromosomal Rearrangements (Gene Fusions)==
 
 
 
Put your text here and fill in the table
 
 
 
{| class="wikitable sortable"
 
 
|-
 
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
!Diagnostic Significance (Yes, No or Unknown)
+
|<span class="blue-text">EXAMPLE:</span> N/A
!Prognostic Significance (Yes, No or Unknown)
+
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
!Therapeutic Significance (Yes, No or Unknown)
+
|<span class="blue-text">EXAMPLE:</span> N/A
!Notes
+
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
 +
|<span class="blue-text">EXAMPLE:</span> D, P, T
 +
|
 +
|
 
|-
 
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|
EXAMPLE 30% (add reference)
+
|
|Yes
+
|
|No
+
|
|Yes
+
|
|EXAMPLE
+
|
 +
|
 +
|
 +
|}
  
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
+
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
|}
 
 
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
 
  
 
No
 
No
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
  
  
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
+
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Individual Region Genomic Gain/Loss/LOH
 
* Individual Region Genomic Gain/Loss/LOH
 
* Characteristic Chromosomal Patterns
 
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
+
* Gene Mutations (SNV/INDEL)}}</blockquote>
  
 
*Diagnosis: <2% blood blasts and <5% bone marrow blasts and persistent cytopenia
 
*Diagnosis: <2% blood blasts and <5% bone marrow blasts and persistent cytopenia
Line 149: Line 143:
 
*Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for RCC patients. This treatment is suitable for patients with monosomy 7 or a complex karyotype in the early stage of the process. Some of the RCC patients benefit from immunosuppressive therapy, although it is unclear whether the immunosuppressive therapy has the risk of relapse long-term<ref>{{Cite journal|last=Hasegawa|first=Daisuke|last2=Manabe|first2=Atsushi|last3=Yagasaki|first3=Hiroshi|last4=Ohtsuka|first4=Yoshitoshi|last5=Inoue|first5=Masami|last6=Kikuchi|first6=Akira|last7=Ohara|first7=Akira|last8=Tsuchida|first8=Masahiro|last9=Kojima|first9=Seiji|date=2009-12|title=Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99)|url=https://pubmed.ncbi.nlm.nih.gov/19499580|journal=Pediatric Blood & Cancer|volume=53|issue=6|pages=1011–1015|doi=10.1002/pbc.22121|issn=1545-5017|pmid=19499580}}</ref><ref>{{Cite journal|last=Yoshimi|first=Ayami|last2=van den Heuvel-Eibrink|first2=Marry M.|last3=Baumann|first3=Irith|last4=Schwarz|first4=Stephan|last5=Simonitsch-Klupp|first5=Ingrid|last6=de Paepe|first6=Pascale|last7=Campr|first7=Vit|last8=Kerndrup|first8=Gitte Birk|last9=O'Sullivan|first9=Maureen|date=2014-04|title=Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood|url=https://pubmed.ncbi.nlm.nih.gov/24162791|journal=Haematologica|volume=99|issue=4|pages=656–663|doi=10.3324/haematol.2013.095786|issn=1592-8721|pmc=3971075|pmid=24162791}}</ref>.
 
*Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for RCC patients. This treatment is suitable for patients with monosomy 7 or a complex karyotype in the early stage of the process. Some of the RCC patients benefit from immunosuppressive therapy, although it is unclear whether the immunosuppressive therapy has the risk of relapse long-term<ref>{{Cite journal|last=Hasegawa|first=Daisuke|last2=Manabe|first2=Atsushi|last3=Yagasaki|first3=Hiroshi|last4=Ohtsuka|first4=Yoshitoshi|last5=Inoue|first5=Masami|last6=Kikuchi|first6=Akira|last7=Ohara|first7=Akira|last8=Tsuchida|first8=Masahiro|last9=Kojima|first9=Seiji|date=2009-12|title=Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99)|url=https://pubmed.ncbi.nlm.nih.gov/19499580|journal=Pediatric Blood & Cancer|volume=53|issue=6|pages=1011–1015|doi=10.1002/pbc.22121|issn=1545-5017|pmid=19499580}}</ref><ref>{{Cite journal|last=Yoshimi|first=Ayami|last2=van den Heuvel-Eibrink|first2=Marry M.|last3=Baumann|first3=Irith|last4=Schwarz|first4=Stephan|last5=Simonitsch-Klupp|first5=Ingrid|last6=de Paepe|first6=Pascale|last7=Campr|first7=Vit|last8=Kerndrup|first8=Gitte Birk|last9=O'Sullivan|first9=Maureen|date=2014-04|title=Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood|url=https://pubmed.ncbi.nlm.nih.gov/24162791|journal=Haematologica|volume=99|issue=4|pages=656–663|doi=10.3324/haematol.2013.095786|issn=1592-8721|pmc=3971075|pmid=24162791}}</ref>.
  
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Individual Region Genomic Gain/Loss/LOH==
 
==Individual Region Genomic Gain/Loss/LOH==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
 
  
 +
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
+
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!Diagnostic Significance (Yes, No or Unknown)
+
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Prognostic Significance (Yes, No or Unknown)
+
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Therapeutic Significance (Yes, No or Unknown)
+
!'''Clinical Relevance Details/Other Notes'''
!Notes
 
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
 
 
 
7
 
7
|EXAMPLE Loss
+
|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
 
 
chr7:1- 159,335,973 [hg38]
 
|EXAMPLE
 
 
 
 
chr7
 
chr7
|Yes
+
|<span class="blue-text">EXAMPLE:</span>
|Yes
+
Unknown
|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span> No
 
+
|<span class="blue-text">EXAMPLE:</span>
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
+
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
 
 
 
8
 
8
|EXAMPLE Gain
+
|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
 
 
chr8:1-145,138,636 [hg38]
 
|EXAMPLE
 
 
 
 
chr8
 
chr8
|No
+
|<span class="blue-text">EXAMPLE:</span>
|No
+
Unknown
|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE
+
|
 
+
|<span class="blue-text">EXAMPLE:</span>
Common recurrent secondary finding for t(8;21) (add reference).
+
Common recurrent secondary finding for t(8;21) (add references).
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span>
 +
17
 +
|<span class="blue-text">EXAMPLE:</span> Amp
 +
|<span class="blue-text">EXAMPLE:</span>
 +
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]
 +
|<span class="blue-text">EXAMPLE:</span>
 +
''ERBB2''
 +
|<span class="blue-text">EXAMPLE:</span> D, P, T
 +
|
 +
|<span class="blue-text">EXAMPLE:</span>
 +
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
  
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
  
 
Monosomy 7 is the most frequent cytogenetic abnormality of RCC patients, followed by trisomy 8 and other abnormalities, including complex karyotypes<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref><ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref><ref>{{Cite journal|last=Gupta|first=Ruchi|last2=Harankhedkar|first2=Shivangi|last3=Rahman|first3=Khaliqur|last4=Singh|first4=Manish K.|last5=Chandra|first5=Dinesh|last6=Mittal|first6=Navkirti|last7=Gupta|first7=Anshul|last8=Nityanand|first8=Soniya|date=2018-10|title=Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review|url=https://pubmed.ncbi.nlm.nih.gov/30369728|journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion|volume=34|issue=4|pages=602–611|doi=10.1007/s12288-018-0941-1|issn=0971-4502|pmc=6186231|pmid=30369728}}</ref>.  
 
Monosomy 7 is the most frequent cytogenetic abnormality of RCC patients, followed by trisomy 8 and other abnormalities, including complex karyotypes<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref><ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref><ref>{{Cite journal|last=Gupta|first=Ruchi|last2=Harankhedkar|first2=Shivangi|last3=Rahman|first3=Khaliqur|last4=Singh|first4=Manish K.|last5=Chandra|first5=Dinesh|last6=Mittal|first6=Navkirti|last7=Gupta|first7=Anshul|last8=Nityanand|first8=Soniya|date=2018-10|title=Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review|url=https://pubmed.ncbi.nlm.nih.gov/30369728|journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion|volume=34|issue=4|pages=602–611|doi=10.1007/s12288-018-0941-1|issn=0971-4502|pmc=6186231|pmid=30369728}}</ref>.  
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
==Characteristic Chromosomal Patterns==
+
==Characteristic Chromosomal or Other Global Mutational Patterns==
  
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
 
  
 +
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Chromosomal Pattern
 
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
+
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
+
!'''Prevalence -'''
!Therapeutic Significance (Yes, No or Unknown)
+
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
!Notes
+
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
 +
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
 +
!'''Clinical Relevance Details/Other Notes'''
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
 
 
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
|Yes
+
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|No
+
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|No
+
|<span class="blue-text">EXAMPLE:</span> D, P
|EXAMPLE:
+
|
 
+
|
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
+
|-
 +
|<span class="blue-text">EXAMPLE:</span>
 +
Microsatellite instability - hypermutated
 +
|
 +
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
 +
|<span class="blue-text">EXAMPLE:</span> P, T
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
  
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
  
 
Monosomy 7 (CCHMC), trisomy 8 and other abnormalities, including complex karyotypes.
 
Monosomy 7 (CCHMC), trisomy 8 and other abnormalities, including complex karyotypes.
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Pictures are needed to be upload!!<br />
 
Pictures are needed to be upload!!<br />
  
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
 
  
 +
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
+
!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
+
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
!Prognostic Significance (Yes, No or Unknown)
+
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
!Therapeutic Significance (Yes, No or Unknown)
+
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Notes
+
!'''Clinical Relevance Details/Other Notes'''
 
|-
 
|-
|EXAMPLE: TP53; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span>''EGFR''
  
EXAMPLE:
+
<br />
 
+
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
EGFR; Exon 20 mutations
+
|<span class="blue-text">EXAMPLE:</span> Oncogene
 
+
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
EXAMPLE: BRAF; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> T
|EXAMPLE: TSG
+
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|EXAMPLE: 20% (COSMIC)
+
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
 
+
|-
EXAMPLE: 30% (add Reference)
+
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
|EXAMPLE: IDH1 R123H
+
<br />
|EXAMPLE: EGFR amplification
+
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
 +
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
 +
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)
 +
|<span class="blue-text">EXAMPLE:</span> P
 +
|
 +
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
 +
|<span class="blue-text">EXAMPLE:</span> Activating mutations
 +
|<span class="blue-text">EXAMPLE:</span> Oncogene
 +
|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
 +
|<span class="blue-text">EXAMPLE:</span> T
 +
|
 +
|
 +
|-
 +
|
 +
|
 +
|
 +
|
 
|
 
|
 
|
 
|
 
|
 
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<br />
 
|}
 
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 
 
 
  
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>
  
 
*Mutations are less common than in adult MDS with a different profile
 
*Mutations are less common than in adult MDS with a different profile
Line 273: Line 314:
 
No
 
No
  
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Epigenomic Alterations==
 
==Epigenomic Alterations==
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==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
+
 
 +
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
+
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 +
|-
 +
|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
 +
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 +
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 
|-
 
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|
|EXAMPLE:  Histone modification, chromatin remodeling
+
|
|EXAMPLE:  Abnormal gene expression program
+
|
 
|}
 
|}
  
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
  
 
*''RAS/MAPK'': involved in ''MAPK'' tyrosine Kinase pathway
 
*''RAS/MAPK'': involved in ''MAPK'' tyrosine Kinase pathway
Line 305: Line 354:
 
*''GATA2'': involved in regulating transcription of genes related with the development and proliferation of hematopoietic and endocrine cell lineages
 
*''GATA2'': involved in regulating transcription of genes related with the development and proliferation of hematopoietic and endocrine cell lineages
  
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
Line 330: Line 382:
  
 
==Familial Forms==
 
==Familial Forms==
 +
  
 
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
 
 
==Additional Information==
 
==Additional Information==
  
Line 339: Line 391:
 
==Links==
 
==Links==
  
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
 
  
 +
Put a link here or anywhere appropriate in this page <span style="color:#0070C0">(''Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
 
==References==
 
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
+
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
  
'''
+
<br />
  
 
==Notes==
 
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage)Additional global feedback or concerns are also welcome.
+
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representativeWhen pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
 +
 
 +
Prior Author(s): 
 +
 
 +
       
 
<nowiki>*</nowiki>''Citation of this Page'': “Childhood myelodysplastic neoplasm with low blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Childhood_myelodysplastic_neoplasm_with_low_blasts</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “Childhood myelodysplastic neoplasm with low blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Childhood_myelodysplastic_neoplasm_with_low_blasts</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]
+
[[Category:HAEM5]]
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[[Category:DISEASE]]
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[[Category:Diseases C]]

Latest revision as of 12:34, 24 March 2025

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Refractory Cytopenia of Childhood.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Myelodysplastic neoplasms
Type Myelodysplastic neoplasms of childhood
Subtype(s) Childhood myelodysplastic neoplasm with low blasts

WHO Essential and Desirable Genetic Diagnostic Criteria

(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

(Instructions: The table will have the related terminology from the WHO autocompleted.)

Acceptable
Not Recommended

Gene Rearrangements

Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE: ABL1 EXAMPLE: BCR::ABL1 EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: Common (CML) EXAMPLE: D, P, T EXAMPLE: Yes (WHO, NCCN) EXAMPLE:

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).

EXAMPLE: CIC EXAMPLE: CIC::DUX4 EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. EXAMPLE: t(4;19)(q25;q13) EXAMPLE: Common (CIC-rearranged sarcoma) EXAMPLE: D EXAMPLE:

DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).

EXAMPLE: ALK EXAMPLE: ELM4::ALK


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. EXAMPLE: N/A EXAMPLE: Rare (Lung adenocarcinoma) EXAMPLE: T EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

EXAMPLE: ABL1 EXAMPLE: N/A EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. EXAMPLE: N/A EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) EXAMPLE: D, P, T
editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.

No

End of V4 Section


editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)
  • Diagnosis: <2% blood blasts and <5% bone marrow blasts and persistent cytopenia
  • Prognosis: In RCC, patients with monosomy 7 have a higher probability of progression[1][2][3]. Patients with trisomy 8 or a normal karyotype are unlikely to progress to advanced MDS.
  • Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for RCC patients. This treatment is suitable for patients with monosomy 7 or a complex karyotype in the early stage of the process. Some of the RCC patients benefit from immunosuppressive therapy, although it is unclear whether the immunosuppressive therapy has the risk of relapse long-term[4][5].
End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE: No EXAMPLE:

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE:

Common recurrent secondary finding for t(8;21) (add references).

EXAMPLE:

17

EXAMPLE: Amp EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

EXAMPLE:

ERBB2

EXAMPLE: D, P, T EXAMPLE:

Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

editv4:Genomic Gain/Loss/LOH
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Monosomy 7 is the most frequent cytogenetic abnormality of RCC patients, followed by trisomy 8 and other abnormalities, including complex karyotypes[6][7][8].

End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T
editv4:Characteristic Chromosomal Aberrations / Patterns
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Monosomy 7 (CCHMC), trisomy 8 and other abnormalities, including complex karyotypes.

Pictures are needed to be upload!!

End of V4 Section

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:EGFR


EXAMPLE: Exon 18-21 activating mutations EXAMPLE: Oncogene EXAMPLE: Common (lung cancer) EXAMPLE: T EXAMPLE: Yes (NCCN) EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations


EXAMPLE: Variable LOF mutations EXAMPLE: Tumor Supressor Gene EXAMPLE: Common (breast cancer) EXAMPLE: P EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations EXAMPLE: Activating mutations EXAMPLE: Oncogene EXAMPLE: Common (melanoma) EXAMPLE: T

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)
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  • Mutations are less common than in adult MDS with a different profile
  • Most frequent mutations: RAS/MAPK, SAMD9/SAMD9L, GATA2[9][10].

Other Mutations

No

End of V4 Section

Epigenomic Alterations

No

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program
editv4:Genes and Main Pathways Involved
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  • RAS/MAPK: involved in MAPK tyrosine Kinase pathway
  • SAMD9/SAMD9L: involved in regulating the growth and proliferation and differentiation of cells
  • GATA2: involved in regulating transcription of genes related with the development and proliferation of hematopoietic and endocrine cell lineages
End of V4 Section

Genetic Diagnostic Testing Methods

Bone marrow minimal histological criteria for refractory cytopenia of childhood[11][12]. Refractory cytopenia of childhood is defined as persistent cytopenia with <5% blasts in bone marrow and <2% blasts in peripheral blood. The criteria of dysplasia must be fulfilled in ≥2 cell lineages or ≥10% of cells within one cell lineage on bone marrow aspirate smears. See table:

Cellularity Erythropoiesis Granulopoiesis Megakaryopoiesis
Variable A few clusters of ≥20 erythroid precursors.

Arrest in maturation, with increased number of proerythroblasts.

Increased number of mitoses.

No minimal diagnostic criteria. Unequivocal micromegakaryocytes;

immunohistochemistry is obligatory (CD61, CD41, CD42b);

other dysplastic changes in variable numbers.

In addition, RCC must be differentiated from aplastic anemia, bone marrow failure syndromes, infection, nutritional deficiencies, and metabolic diseases.

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

Put a link here or anywhere appropriate in this page (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)

  1. Passmore, S. Jane; et al. (2003-06). "Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival". British Journal of Haematology. 121 (5): 758–767. doi:10.1046/j.1365-2141.2003.04361.x. ISSN 0007-1048. PMID 12780790. Check date values in: |date= (help)
  2. Pui, Ching-Hon; et al. (2004). "Childhood and adolescent lymphoid and myeloid leukemia". Hematology. American Society of Hematology. Education Program: 118–145. doi:10.1182/asheducation-2004.1.118. ISSN 1520-4391. PMID 15561680.
  3. Kardos, Gabriela; et al. (2003-09-15). "Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7". Blood. 102 (6): 1997–2003. doi:10.1182/blood-2002-11-3444. ISSN 0006-4971. PMID 12763938.
  4. Hasegawa, Daisuke; et al. (2009-12). "Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99)". Pediatric Blood & Cancer. 53 (6): 1011–1015. doi:10.1002/pbc.22121. ISSN 1545-5017. PMID 19499580. Check date values in: |date= (help)
  5. Yoshimi, Ayami; et al. (2014-04). "Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood". Haematologica. 99 (4): 656–663. doi:10.3324/haematol.2013.095786. ISSN 1592-8721. PMC 3971075. PMID 24162791. Check date values in: |date= (help)
  6. Kardos, Gabriela; et al. (2003-09-15). "Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7". Blood. 102 (6): 1997–2003. doi:10.1182/blood-2002-11-3444. ISSN 0006-4971. PMID 12763938.
  7. Niemeyer, Charlotte M.; et al. (2011). "Classification of childhood aplastic anemia and myelodysplastic syndrome". Hematology. American Society of Hematology. Education Program. 2011: 84–89. doi:10.1182/asheducation-2011.1.84. ISSN 1520-4383. PMID 22160017.
  8. Gupta, Ruchi; et al. (2018-10). "Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review". Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion. 34 (4): 602–611. doi:10.1007/s12288-018-0941-1. ISSN 0971-4502. PMC 6186231. PMID 30369728. Check date values in: |date= (help)
  9. Schwartz, Jason R.; et al. (2017-11-16). "The genomic landscape of pediatric myelodysplastic syndromes". Nature Communications. 8 (1): 1557. doi:10.1038/s41467-017-01590-5. ISSN 2041-1723. PMC 5691144. PMID 29146900.
  10. Wlodarski, Marcin W.; et al. (2016-03-17). "Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents". Blood. 127 (11): 1387–1397, quiz 1518. doi:10.1182/blood-2015-09-669937. ISSN 1528-0020. PMID 26702063.
  11. Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.
  12. Iwafuchi, Hideto (2018). "The histopathology of bone marrow failure in children". Journal of clinical and experimental hematopathology: JCEH. 58 (2): 68–86. doi:10.3960/jslrt.18018. ISSN 1880-9952. PMC 6413145. PMID 29998978.


Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):


*Citation of this Page: “Childhood myelodysplastic neoplasm with low blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/24/2025, https://ccga.io/index.php/HAEM5:Childhood_myelodysplastic_neoplasm_with_low_blasts.