Changes

{{Under Construction}}

{{Under Construction}}

<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:Acute Myeloid Leukemia (AML) with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM]].

<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:Acute Myeloid Leukemia (AML) with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM]].

}}</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 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)*==

Gordana Raca MD PhD, University of Southern California, Los Angeles

Gordana Raca MD PhD, University of Southern California, Los Angeles

[[File:inv(3)(q21q26.2).png|inv(3)(q21q26.2)]]

[[File:inv(3)(q21q26.2).png|inv(3)(q21q26.2)]]

[[File:t(3;3)(q21;q26.2).png|t(3;3)(q21;q26.2)]]

[[File:t(3;3)(q21;q26.2).png|t(3;3)(q21;q26.2)]]

|}

|}

==Definition / Description of Disease==

==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>

The  inv(3)(q21q26.2)/t(3;3)(q21;q26.2) defines a distinctive cytogenetic subtype of acute myeloid leukemia (AML) in 2008 WHO classification (AML with inv(3)(q21q26.2)/t(3;3)(q21;q26.2), although it is currently not recognized as an abnormality pathognomonic for diagnosis of  AML irrespective of blast percentage. This abnormality also occurs in myelodysplastic syndrome (MDS), where it is associated with aggressive course and a high risk of progression to AML. It can also rarely be found in other myeloid neoplasms, including chronic myelogenous leukemia (mostly during accelerated phase or in blast crisis), other myeloproliferative neoplasms (MPN), and in overlap MDS/MPNs including chronic myelomonocytic leukemia<ref name=":0">{{Cite journal|last=Rogers|first=Heesun J.|last2=Vardiman|first2=James W.|last3=Anastasi|first3=John|last4=Raca|first4=Gordana|last5=Savage|first5=Natasha M.|last6=Cherry|first6=Athena M.|last7=Arber|first7=Daniel|last8=Moore|first8=Erika|last9=Morrissette|first9=Jennifer J. D.|date=2014|title=Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study|url=https://www.ncbi.nlm.nih.gov/pubmed/24463215|journal=Haematologica|volume=99|issue=5|pages=821–829|doi=10.3324/haematol.2013.096420|issn=1592-8721|pmc=4008101|pmid=24463215}}</ref>.

{| class="wikitable"

 

|+

inv(3)(q21q26.2) and t(3;3)(q21;q26.2) are variant rearrangements with similar consequences at the molecular level and similar disease associations and clinical implications. 

|WHO Essential Criteria (Genetics)*

 

|

In addition to the balanced inversion and translocation involving the bands 3q21 and 3q26.2, other 3q abnormalities are also common in AML.  A study of 6515 adults with newly diagnosed AML detected 3q abnormalities in 4.4% of the patients, and classified them in four categories<ref name=":1">{{Cite journal|last=Lugthart|first=Sanne|last2=Gröschel|first2=Stefan|last3=Beverloo|first3=H. Berna|last4=Kayser|first4=Sabine|last5=Valk|first5=Peter J. M.|last6=van Zelderen-Bhola|first6=Shama Lydia|last7=Jan Ossenkoppele|first7=Gert|last8=Vellenga|first8=Edo|last9=van den Berg-de Ruiter|first9=Eva|date=2010|title=Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/20660833|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=24|pages=3890–3898|doi=10.1200/JCO.2010.29.2771|issn=1527-7755|pmid=20660833}}</ref>:  

|-

 

|WHO Desirable Criteria (Genetics)*

|

#Translocations involving only the band 3q26.2

|-

#Translocations involving only the band 3q21

|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==

==Synonyms / Terminology==

<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>

 

==Epidemiology / Prevalence==

 

AML with inv(3)(q21q26.2) and t(3;3)(q21;q26.2) comprises 1-2.5% of all AML cases and less than 1% of all MDS cases<ref name=":0" /><ref name=":1" />.

 

==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

 

 

 

|-

|-

|'''Laboratory Findings'''

|Not Recommended

|<span class="blue-text">EXAMPLE:</span> Cytopenias

|

 

|}

|}

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Finding!!Marker

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

|-

|-

|Positive (universal)||<span class="blue-text">EXAMPLE:</span> 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

|-

|-

|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2

|<span class="blue-text">EXAMPLE:</span> ''CIC''

|-

|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''

|Negative (universal)||<span class="blue-text">EXAMPLE:</span> 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>

 

|-

|-

|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4

|<span class="blue-text">EXAMPLE:</span> ''ALK''

|}

|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''

Put your text here and fill in the table

|<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.

|-

|-

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!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.

|<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)

|

|

|Yes

|

|No

|

|Yes

|

|<span class="blue-text">EXAMPLE:</span>

|

 

|

|

|}

|}

<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

BCR-ABL1 positive patients with CML and concomitant MECOM rearrangement are considered in an aggressive phase of CML (Accelerated Phase) rather than de novo AML with inv(3)/t(3;3)

BCR-ABL1 positive patients with CML and concomitant MECOM rearrangement are considered in an aggressive phase of CML (Accelerated Phase) rather than de novo AML with inv(3)/t(3;3)

Prognostic: The inv(3)(q21q26.2)/t(3;3)(q21;q26.2)  is associated with a dismal prognosis in both AML and MDS. Review of  6515 adult patients with newly diagnosed AML enrolled in prospective European trials showed 5-year OS of only 5.7% +/- 3 for AML with inv(3)/t(3;3), with the median survival os 10.3 months. This adverse prognostic impact of inv(3)/t(3;3) appears to be further enhanced by additional monosomy 7 and/or complex karyotype. Similarly, the prognosis of MDS with inv(3)/t(3;3) is also poor, and the revised International Prognostic Scoring System (IPSS-R) for MDS includes inv(3)/t(3;3) among its poor risk cytogenetic abnormalities<ref name=":0" /><ref name=":1" />.

Prognostic: The inv(3)(q21q26.2)/t(3;3)(q21;q26.2)  is associated with a dismal prognosis in both AML and MDS. Review of  6515 adult patients with newly diagnosed AML enrolled in prospective European trials showed 5-year OS of only 5.7% +/- 3 for AML with inv(3)/t(3;3), with the median survival os 10.3 months. This adverse prognostic impact of inv(3)/t(3;3) appears to be further enhanced by additional monosomy 7 and/or complex karyotype. Similarly, the prognosis of MDS with inv(3)/t(3;3) is also poor, and the revised International Prognostic Scoring System (IPSS-R) for MDS includes inv(3)/t(3;3) among its poor risk cytogenetic abnormalities<ref name=":0">{{Cite journal|last=Rogers|first=Heesun J.|last2=Vardiman|first2=James W.|last3=Anastasi|first3=John|last4=Raca|first4=Gordana|last5=Savage|first5=Natasha M.|last6=Cherry|first6=Athena M.|last7=Arber|first7=Daniel|last8=Moore|first8=Erika|last9=Morrissette|first9=Jennifer J. D.|date=2014|title=Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study|url=https://www.ncbi.nlm.nih.gov/pubmed/24463215|journal=Haematologica|volume=99|issue=5|pages=821–829|doi=10.3324/haematol.2013.096420|issn=1592-8721|pmc=4008101|pmid=24463215}}</ref><ref name=":1">{{Cite journal|last=Lugthart|first=Sanne|last2=Gröschel|first2=Stefan|last3=Beverloo|first3=H. Berna|last4=Kayser|first4=Sabine|last5=Valk|first5=Peter J. M.|last6=van Zelderen-Bhola|first6=Shama Lydia|last7=Jan Ossenkoppele|first7=Gert|last8=Vellenga|first8=Edo|last9=van den Berg-de Ruiter|first9=Eva|date=2010|title=Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/20660833|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=24|pages=3890–3898|doi=10.1200/JCO.2010.29.2771|issn=1527-7755|pmid=20660833}}</ref>.

Therapeutic: AML with inv(3)(q21q26.2) or t(3;3) (q21;q26.2) is an aggressive disease with short survival, in need for novel and more efficient treatments. Some studies have shown that arsenic trioxide induces targeted specific degradation of the AML1/MDS1/EVI1 oncoprotein, and an isolated case report described  good response to Arsenic trioxide and thalidomide combination in a patient with MDS with inv(3)<ref>{{Cite journal|last=Shackelford|first=David|last2=Kenific|first2=Candia|last3=Blusztajn|first3=Agnieszka|last4=Waxman|first4=Samuel|last5=Ren|first5=Ruibao|date=2006|title=Targeted degradation of the AML1/MDS1/EVI1 oncoprotein by arsenic trioxide|url=https://www.ncbi.nlm.nih.gov/pubmed/17145882|journal=Cancer Research|volume=66|issue=23|pages=11360–11369|doi=10.1158/0008-5472.CAN-06-1774|issn=0008-5472|pmid=17145882}}</ref><ref>{{Cite journal|last=Raza|first=Azra|last2=Buonamici|first2=Silvia|last3=Lisak|first3=Laurie|last4=Tahir|first4=Sarah|last5=Li|first5=Donglan|last6=Imran|first6=Mehnaz|last7=Chaudary|first7=Nusrat Ijaz|last8=Pervaiz|first8=Hassan|last9=Gallegos|first9=J. Alejandro|date=2004|title=Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression|url=https://www.ncbi.nlm.nih.gov/pubmed/15203277|journal=Leukemia Research|volume=28|issue=8|pages=791–803|doi=10.1016/j.leukres.2003.11.018|issn=0145-2126|pmid=15203277}}</ref>.

Therapeutic: AML with inv(3)(q21q26.2) or t(3;3) (q21;q26.2) is an aggressive disease with short survival, in need for novel and more efficient treatments. Some studies have shown that arsenic trioxide induces targeted specific degradation of the AML1/MDS1/EVI1 oncoprotein, and an isolated case report described  good response to Arsenic trioxide and thalidomide combination in a patient with MDS with inv(3)<ref>{{Cite journal|last=Shackelford|first=David|last2=Kenific|first2=Candia|last3=Blusztajn|first3=Agnieszka|last4=Waxman|first4=Samuel|last5=Ren|first5=Ruibao|date=2006|title=Targeted degradation of the AML1/MDS1/EVI1 oncoprotein by arsenic trioxide|url=https://www.ncbi.nlm.nih.gov/pubmed/17145882|journal=Cancer Research|volume=66|issue=23|pages=11360–11369|doi=10.1158/0008-5472.CAN-06-1774|issn=0008-5472|pmid=17145882}}</ref><ref>{{Cite journal|last=Raza|first=Azra|last2=Buonamici|first2=Silvia|last3=Lisak|first3=Laurie|last4=Tahir|first4=Sarah|last5=Li|first5=Donglan|last6=Imran|first6=Mehnaz|last7=Chaudary|first7=Nusrat Ijaz|last8=Pervaiz|first8=Hassan|last9=Gallegos|first9=J. Alejandro|date=2004|title=Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression|url=https://www.ncbi.nlm.nih.gov/pubmed/15203277|journal=Leukemia Research|volume=28|issue=8|pages=791–803|doi=10.1016/j.leukres.2003.11.018|issn=0145-2126|pmid=15203277}}</ref>.

----

----

</blockquote>

</blockquote>

==Individual Region Genomic Gain / Loss / LOH==

==Individual Region Genomic Gain/Loss/LOH==

{| 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>

 

|<span class="blue-text">EXAMPLE:</span> D, P

|<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>

 

chr8:1-145,138,636 [hg38]

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

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

 

|<span class="blue-text">EXAMPLE:</span> D, P, T

|

|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=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

Put your text here.

Put your text here.

----

----

</blockquote>

</blockquote>

==Characteristic Chromosomal Patterns==

==Characteristic Chromosomal or Other Global Mutational Patterns==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Chromosomal Pattern

!Chromosomal Pattern

!Diagnostic Significance (Yes, No or Unknown)

!Molecular Pathogenesis

!Prognostic Significance (Yes, No or Unknown)

!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>

 

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)

|}

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>

<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 is the most common associated (secondary) cytogenetic abnormality (in ~66% of cases), and appears to further contribute to the adverse prognosis of the inv(3q)/t(3;3) abnormality<ref name=":0" /><ref name=":1" />.

Monosomy 7 is the most common associated (secondary) cytogenetic abnormality (in ~66% of cases), and appears to further contribute to the adverse prognosis of the inv(3q)/t(3;3) abnormality<ref name=":0" /><ref name=":1" />.

----

----

</blockquote>

</blockquote>

==Gene Mutations (SNV / INDEL)==

==Gene Mutations (SNV/INDEL)==

{| 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  '''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!Notes

!'''Clinical Relevance Details/Other Notes'''

|-

|-

|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span>''EGFR''

<span class="blue-text">EXAMPLE:</span>

 

EGFR; Exon 20 mutations

 

<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations

|<span class="blue-text">EXAMPLE:</span> T

|<span class="blue-text">EXAMPLE:</span> TSG

|<span class="blue-text">EXAMPLE:</span> 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).

 

<span class="blue-text">EXAMPLE:</span> 30% (add Reference)

|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span> IDH1 R123H

|<span class="blue-text">EXAMPLE:</span> 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> >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

|

|

|

|

|

|

|}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.

|}

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>

<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>

Secondary mutations are found in all AML cases with inv(3) ot t(3;3). Mutations in genes activating RAS/TK signaling pathway are the most common mutation.

Secondary mutations are found in all AML cases with inv(3) ot t(3;3). Mutations in genes activating RAS/TK signaling pathway are the most common mutation.

</blockquote>

</blockquote>

==Epigenomic Alterations==

==Epigenomic Alterations==

Put your text here

Put your text here

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>

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

|-

|-

|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations

|<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

|-

|-

|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations

|<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

|-

|-

|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span> ''KMT2C'' and ''ARID1A''; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program

|<span class="blue-text">EXAMPLE:</span> 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>

<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>

The ''[[MECOM]]'' (MDS1 and EVI1 complex locus)  gene in 3q26.3 is the key gene implicated in pathogenesis of AML with inv(3)/t(3;3). ''MECOM'' codes for several differentially spliced transcripts: MDS1-EVI1, MDS1 and EVI1. It consequently yields the MDS1-EVI1 [1239 amino acids (AA)], MDS1 (188AA) and EVI1 (1051AA) protein isoforms. While ''EVI1'' deregulated expression has been reported to be critical in stem cell self-renewal and leukaemogenesis, the roles of ''MDS1'' and MDS1-EVI1 in haematological malignancies remain unclear<ref name=":2">{{Cite journal|last=Wieser|first=Rotraud|date=2007|title=The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions|url=https://www.ncbi.nlm.nih.gov/pubmed/17507183|journal=Gene|volume=396|issue=2|pages=346–357|doi=10.1016/j.gene.2007.04.012|issn=0378-1119|pmid=17507183}}</ref>.  

The ''[[MECOM]]'' (MDS1 and EVI1 complex locus)  gene in 3q26.3 is the key gene implicated in pathogenesis of AML with inv(3)/t(3;3). ''MECOM'' codes for several differentially spliced transcripts: MDS1-EVI1, MDS1 and EVI1. It consequently yields the MDS1-EVI1 [1239 amino acids (AA)], MDS1 (188AA) and EVI1 (1051AA) protein isoforms. While ''EVI1'' deregulated expression has been reported to be critical in stem cell self-renewal and leukaemogenesis, the roles of ''MDS1'' and MDS1-EVI1 in haematological malignancies remain unclear<ref name=":2">{{Cite journal|last=Wieser|first=Rotraud|date=2007|title=The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions|url=https://www.ncbi.nlm.nih.gov/pubmed/17507183|journal=Gene|volume=396|issue=2|pages=346–357|doi=10.1016/j.gene.2007.04.012|issn=0378-1119|pmid=17507183}}</ref>.  

==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==

==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 />

==Notes==

==Notes==

<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with MECOM rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_MECOM_rearrangement</nowiki>.

<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with MECOM rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_MECOM_rearrangement</nowiki>.

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases A]]