Compendium of Cancer Genome Aberrations

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HAEM5:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion (view source)

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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1]].
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<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:B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1]].
 
}}</blockquote>
 
}}</blockquote>
   −
<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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 to a table, click nearby within the table and select the > symbol that appears to be given options. 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>
+
<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)*==
 
Afia Hasnain, MBBS, PhD; Yassmine Akkari, PhD, FACMG
 
Afia Hasnain, MBBS, PhD; Yassmine Akkari, PhD, FACMG
−
__TOC__
+
==WHO Classification of Disease==
   −
==Cancer Category / Type==
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{| class="wikitable"
 +
!Structure
 +
!Disease
 +
|-
 +
|Book
 +
|Haematolymphoid Tumours (5th ed.)
 +
|-
 +
|Category
 +
|B-cell lymphoid proliferations and lymphomas
 +
|-
 +
|Family
 +
|Precursor B-cell neoplasms
 +
|-
 +
|Type
 +
|B-lymphoblastic leukaemias/lymphomas
 +
|-
 +
|Subtype(s)
 +
|B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion
 +
|}
   −
B-Lymphoblastic Leukemia/Lymphoma
+
==WHO Essential and Desirable Genetic Diagnostic Criteria==
−
 
+
<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>
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==Cancer Sub-Classification / Subtype==
+
{| class="wikitable"
−
 
+
|+
−
B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); ''BCR-ABL1''
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|WHO Essential Criteria (Genetics)*
−
 
+
|
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==Definition / Description of Disease==
+
|-
−
 
+
|WHO Desirable Criteria (Genetics)*
−
B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2) is a neoplasm of lymphoblasts committed to the B-cell lineage in which the blasts harbor a translocation between ''BCR'' at 22q11.2 and ''ABL1'' oncogene at 9q34.1. The t(9;22) results in the production of a ''BCR-ABL1'' fusion, also known as the Philadelphia chromosome (Ph+).  
+
|
−
 
+
|-
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==Synonyms / Terminology==
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|Other Classification
−
 
+
|
−
* Philadelphia chromosome
+
|}
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* Ph+
+
<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>].
−
 
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==Related Terminology==
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==Epidemiology / Prevalence==
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<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
−
 
  −
* most common genomic alteration in adult B-ALL (25–30%)
  −
 
  −
* detected in only 2–4% of pediatric cases
  −
 
  −
==Clinical Features==
  −
 
  −
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
   
{| class="wikitable"
 
{| class="wikitable"
−
|'''Signs and Symptoms'''
+
|+
−
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
+
|Acceptable
−
 
+
|
−
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
  −
 
  −
<span class="blue-text">EXAMPLE:</span> Fatigue
  −
 
  −
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
   
|-
 
|-
−
|'''Laboratory Findings'''
+
|Not Recommended
−
|<span class="blue-text">EXAMPLE:</span> Cytopenias
+
|
−
 
  −
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
   
|}
 
|}
    +
==Gene Rearrangements==
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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
  −
  −
The presenting features are generally similar to those seen in patients with other B-ALLs. Most children with B-ALL with ''BCR-ABL1'' are considered to have high risk on the basis of age and white blood cell count (WBC). Patients tend to have a high WBC count at presentation, and although they may have organ involvement, lymphomatous presentations are rare.
  −
  −
</blockquote>
  −
==Sites of Involvement==
  −
  −
Bone marrow
  −
  −
==Morphologic Features==
  −
  −
Put your text here
  −
  −
==Immunophenotype==
  −
  −
Put your text here and/or fill in the table
      +
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)||CD10, CD19 and TdT
+
|<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)||CD13, CD33 and CD25 (in adults)
+
|<span class="blue-text">EXAMPLE:</span> ''CIC''
−
|-
+
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
−
|Negative (universal)||KIT (CD117)
+
|<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)||<span class="blue-text">EXAMPLE:</span> CD4
+
|<span class="blue-text">EXAMPLE:</span> ''ALK''
−
|}
+
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
   −
==Chromosomal Rearrangements (Gene Fusions)==
     −
Put your text here and fill in the table
+
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.
 +
|<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>
   −
{| class="wikitable sortable"
+
Both balanced and unbalanced forms are observed by FISH (add references).
 
|-
 
|-
−
!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
 +
|
 +
|
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|
−
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
+
|
−
|Yes
+
|
−
|No
+
|
−
|Yes
+
|
−
|<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).
+
|
−
|}
+
|}
−
     −
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
    
Put your text here and/or fill in the table
 
Put your text here and/or fill in the table
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|}
 
|}
 
 
 +
<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
 +
----
 
</blockquote>
 
</blockquote>
      −
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|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>
    
The pediatric and adult Ph + B-ALL has been associated with the worst prognosis of the major cytogenetic subtypes of B- ALL. However, therapy with tyrosine kinase inhibitors (TKIs) has had a significantly favorable effect on outcome. A major molecular response is defined as a ≥3-log reduction in BCR-ABL1 transcript compared with the standardized baseline.  
 
The pediatric and adult Ph + B-ALL has been associated with the worst prognosis of the major cytogenetic subtypes of B- ALL. However, therapy with tyrosine kinase inhibitors (TKIs) has had a significantly favorable effect on outcome. A major molecular response is defined as a ≥3-log reduction in BCR-ABL1 transcript compared with the standardized baseline.  
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The presence of IKZF1 deletion has been associated with poor outcome and high risk of re- lapse. <ref>{{Cite journal|last=van der Veer|first=Arian|last2=Zaliova|first2=Marketa|last3=Mottadelli|first3=Federica|last4=De Lorenzo|first4=Paola|last5=Te Kronnie|first5=Gertruuy|last6=Harrison|first6=Christine J.|last7=Cavé|first7=Hélène|last8=Trka|first8=Jan|last9=Saha|first9=Vaskar|date=2014-03-13|title=IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL|url=https://pubmed.ncbi.nlm.nih.gov/24366361|journal=Blood|volume=123|issue=11|pages=1691–1698|doi=10.1182/blood-2013-06-509794|issn=1528-0020|pmid=24366361}}</ref>
 
The presence of IKZF1 deletion has been associated with poor outcome and high risk of re- lapse. <ref>{{Cite journal|last=van der Veer|first=Arian|last2=Zaliova|first2=Marketa|last3=Mottadelli|first3=Federica|last4=De Lorenzo|first4=Paola|last5=Te Kronnie|first5=Gertruuy|last6=Harrison|first6=Christine J.|last7=Cavé|first7=Hélène|last8=Trka|first8=Jan|last9=Saha|first9=Vaskar|date=2014-03-13|title=IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL|url=https://pubmed.ncbi.nlm.nih.gov/24366361|journal=Blood|volume=123|issue=11|pages=1691–1698|doi=10.1182/blood-2013-06-509794|issn=1528-0020|pmid=24366361}}</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. Do not delete table.'') </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
   
|-
 
|-
 
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
   
7
 
7
 
|<span class="blue-text">EXAMPLE:</span> Loss
 
|<span class="blue-text">EXAMPLE:</span> Loss
 
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
 
+
chr7
−
chr7:1- 159,335,973 [hg38]
   
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
 
+
Unknown
−
chr7
+
|<span class="blue-text">EXAMPLE:</span> D, P
−
|Yes
+
|<span class="blue-text">EXAMPLE:</span> No
−
|Yes
  −
|No
   
|<span class="blue-text">EXAMPLE:</span>
 
|<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 references).
−
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).
   
|-
 
|-
 
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
   
8
 
8
 
|<span class="blue-text">EXAMPLE:</span> Gain
 
|<span class="blue-text">EXAMPLE:</span> Gain
 
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
 
+
chr8
−
chr8:1-145,138,636 [hg38]
+
|<span class="blue-text">EXAMPLE:</span>
 +
Unknown
 +
|<span class="blue-text">EXAMPLE:</span> D, P
 +
|
 +
|<span class="blue-text">EXAMPLE:</span>
 +
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>
 
|<span class="blue-text">EXAMPLE:</span>
−
 
+
''ERBB2''
−
chr8
+
|<span class="blue-text">EXAMPLE:</span> D, P, T
−
|No
+
|
−
|No
  −
|No
   
|<span class="blue-text">EXAMPLE:</span>
 
|<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.
−
Common recurrent secondary finding for t(8;21) (add reference).
+
|-
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 +
|
 
|}
 
|}
   −
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
    
The most common accompanying chromosomal abnormalities include monosomy 7 (including deletion of the IKZF1 gene) (18%), monosomy 9 or 9p deletion (9%), and gain of 1q (8%).  
 
The most common accompanying chromosomal abnormalities include monosomy 7 (including deletion of the IKZF1 gene) (18%), monosomy 9 or 9p deletion (9%), and gain of 1q (8%).  
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|}
 
|}
 
 
 +
<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. Do not delete table.'')</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'''
 
|-
 
|-
 
|<span class="blue-text">EXAMPLE:</span>
 
|<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
 +
|
 +
|
 +
|-
 
|<span class="blue-text">EXAMPLE:</span>
 
|<span class="blue-text">EXAMPLE:</span>
−
 
+
Microsatellite instability - hypermutated
−
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> Common (Endometrial carcinoma)
 +
|<span class="blue-text">EXAMPLE:</span> P, T
 +
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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
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<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>
    
The t(9;22) results in the production of a BCR-ABL1 fusion protein. The majority of pediatric and half of adult t(9;22) positive B-ALL involve the minor breakpoint cluster region (m-bcr) encoding a smaller p190 fusion protein in contrast to chronic myelogenous leukemia (CML), where it involves the major breakpoint cluster region (M-bcr). <ref>{{Cite journal|last=Woo|first=Jennifer S.|last2=Alberti|first2=Michael O.|last3=Tirado|first3=Carlos A.|date=2014|title=Childhood B-acute lymphoblastic leukemia: a genetic update|url=https://pubmed.ncbi.nlm.nih.gov/24949228|journal=Experimental Hematology & Oncology|volume=3|pages=16|doi=10.1186/2162-3619-3-16|issn=2162-3619|pmc=4063430|pmid=24949228}}</ref>
 
The t(9;22) results in the production of a BCR-ABL1 fusion protein. The majority of pediatric and half of adult t(9;22) positive B-ALL involve the minor breakpoint cluster region (m-bcr) encoding a smaller p190 fusion protein in contrast to chronic myelogenous leukemia (CML), where it involves the major breakpoint cluster region (M-bcr). <ref>{{Cite journal|last=Woo|first=Jennifer S.|last2=Alberti|first2=Michael O.|last3=Tirado|first3=Carlos A.|date=2014|title=Childhood B-acute lymphoblastic leukemia: a genetic update|url=https://pubmed.ncbi.nlm.nih.gov/24949228|journal=Experimental Hematology & Oncology|volume=3|pages=16|doi=10.1186/2162-3619-3-16|issn=2162-3619|pmc=4063430|pmid=24949228}}</ref>
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<blockquote class="blockedit">
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<center><span style="color:Maroon">'''End of V4 Section'''</span>
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----
 
</blockquote>
 
</blockquote>
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==Gene Mutations (SNV / INDEL)==
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==Gene Mutations (SNV/INDEL)==
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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 as 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. Do not delete table.'') </span>
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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"
 
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!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
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!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
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!'''Diagnostic Significance (Yes, No or Unknown)'''
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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
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!Prognostic Significance (Yes, No or Unknown)
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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
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!Therapeutic Significance (Yes, No or Unknown)
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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
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!Notes
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!'''Clinical Relevance Details/Other Notes'''
 
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|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
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|<span class="blue-text">EXAMPLE:</span>''EGFR''
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<span class="blue-text">EXAMPLE:</span>
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|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations
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EGFR; Exon 20 mutations
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|<span class="blue-text">EXAMPLE:</span> Oncogene
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|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)
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<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
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|<span class="blue-text">EXAMPLE:</span> T
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|<span class="blue-text">EXAMPLE:</span> TSG
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|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
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|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
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|<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).
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<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
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|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
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|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
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<br />
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|<span class="blue-text">EXAMPLE:</span> EGFR amplification
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|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations
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|<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
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|<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.
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|-
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|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
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|<span class="blue-text">EXAMPLE:</span> Activating mutations
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|<span class="blue-text">EXAMPLE:</span> Oncogene
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|<span class="blue-text">EXAMPLE:</span> Common (melanoma)
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|<span class="blue-text">EXAMPLE:</span> T
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|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
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|}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.
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<br />
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==Epigenomic Alterations==
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|}
  −
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.
     −
==Epigenomic Alterations==
      
Put your text here
 
Put your text here
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==Genes and Main Pathways Involved==
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==Genes and Main Pathways Involved==
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
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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"
 
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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
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|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
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|<span class="blue-text">EXAMPLE:</span> ''BRAF'' and ''MAP2K1''; Activating mutations
 
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
 
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
 
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
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|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
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|<span class="blue-text">EXAMPLE:</span> ''CDKN2A''; Inactivating mutations
 
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
 
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
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|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
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|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations
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|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
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|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
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|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
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|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
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<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
    
''BCR'' and ''ABL1''
 
''BCR'' and ''ABL1''
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<blockquote class="blockedit">
 +
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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----
 
</blockquote>
 
</blockquote>
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
   −
* Clinical testing for the ''BCR-ABL1'' fusion includes conventional chromosome studies, dual color, dual fusion FISH analysis and RT- PCR.  
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*Clinical testing for the ''BCR-ABL1'' fusion includes conventional chromosome studies, dual color, dual fusion FISH analysis and RT- PCR.
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* FISH results can be available within 24 h and should be considered as the first line test.
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*FISH results can be available within 24 h and should be considered as the first line test.
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* Quantitative RT-PCR can detect specific transcripts at a higher sensitivity, and important at follow up to determine disease status and degree of response.  
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*Quantitative RT-PCR can detect specific transcripts at a higher sensitivity, and important at follow up to determine disease status and degree of response.
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* Conventional cytogenetics can also detect variant translocations, additional Philadelphia chromosome resulting in gain of 9q and 22q as well as trisomy 8, and a hyperdiploid karyotype.
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*Conventional cytogenetics can also detect variant translocations, additional Philadelphia chromosome resulting in gain of 9q and 22q as well as trisomy 8, and a hyperdiploid karyotype.
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* CMA cannot detect balanced rearrangements such as t(9;22) but it can detect additional copy number abnormalities.  
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*CMA cannot detect balanced rearrangements such as t(9;22) but it can detect additional copy number abnormalities.
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* An average of 7.8 lesions per case were observed by using CMA in adults with Ph + B-ALL.<ref>{{Cite journal|last=Fedullo|first=Anna Lucia|last2=Messina|first2=Monica|last3=Elia|first3=Loredana|last4=Piciocchi|first4=Alfonso|last5=Gianfelici|first5=Valentina|last6=Lauretti|first6=Alessia|last7=Soddu|first7=Stefano|last8=Puzzolo|first8=Maria Cristina|last9=Minotti|first9=Clara|date=02 2019|title=Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30190342|journal=Haematologica|volume=104|issue=2|pages=312–318|doi=10.3324/haematol.2018.196055|issn=1592-8721|pmc=6355475|pmid=30190342}}</ref>
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*An average of 7.8 lesions per case were observed by using CMA in adults with Ph + B-ALL.<ref>{{Cite journal|last=Fedullo|first=Anna Lucia|last2=Messina|first2=Monica|last3=Elia|first3=Loredana|last4=Piciocchi|first4=Alfonso|last5=Gianfelici|first5=Valentina|last6=Lauretti|first6=Alessia|last7=Soddu|first7=Stefano|last8=Puzzolo|first8=Maria Cristina|last9=Minotti|first9=Clara|date=02 2019|title=Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30190342|journal=Haematologica|volume=104|issue=2|pages=312–318|doi=10.3324/haematol.2018.196055|issn=1592-8721|pmc=6355475|pmid=30190342}}</ref>
    
==Familial Forms==
 
==Familial Forms==
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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>
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==Additional Information==
 
==Additional Information==
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==References==
 
==References==
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(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 />
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(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 />
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'''
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<br />
    
==Notes==
 
==Notes==
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<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.
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<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 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.
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Prior Author(s): 
 +
 
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<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1_fusion</nowiki>.
 
<nowiki>*</nowiki>''Citation of this Page'': “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1_fusion</nowiki>.
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[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases B]]
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[[Category:HAEM5]]
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[[Category:DISEASE]]
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[[Category:Diseases B]]
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