Compendium of Cancer Genome Aberrations

HAEM5:Acute myeloid leukaemia with DEK::NUP214 fusion: Difference between revisions

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{{DISPLAYTITLE:Acute myeloid leukaemia with DEK::NUP214 fusion}}
{{DISPLAYTITLE:Acute myeloid leukaemia with DEK::NUP214 fusion}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-04. The original page can be found at [[HAEM4:Acute Myeloid Leukemia (AML) with t(6;9)(p23;q34.1); DEK-NUP214]].
}}</blockquote>
==Primary Author(s)*==
==Primary Author(s)*==


Jennelle C. Hodge, PhD, FACMG
Jennelle C. Hodge, PhD, FACMG


__TOC__
==WHO Classification of Disease==
 
[[File:T(6;9)(p23;q34).png]]
 
==Cancer Category / Type==
 
[[AML|Acute Myeloid Leukemia]]
 
==Cancer Sub-Classification / Subtype==
 
Acute myeloid leukemia (AML) with t(6;9)(p23;q34.1) resulting in DEK-NUP214 fusion
 
==Definition / Description of Disease==
 
This is a distinct entity in the World Health Organization (WHO) classification system, and the most common associated French-American-British (FAB) classifications are M2, M4 and M1<ref name=":0">Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization 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, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p137-138.</ref><ref>{{Cite journal|last=Oyarzo|first=Mauricio P.|last2=Lin|first2=Pei|last3=Glassman|first3=Armand|last4=Bueso-Ramos|first4=Carlos E.|last5=Luthra|first5=Rajyalakshmi|last6=Medeiros|first6=L. Jeffrey|date=2004|title=Acute myeloid leukemia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of flt3 gene mutations|url=https://www.ncbi.nlm.nih.gov/pubmed/15362364|journal=American Journal of Clinical Pathology|volume=122|issue=3|pages=348–358|doi=10.1309/5DGB-59KQ-A527-PD47|issn=0002-9173|pmid=15362364}}</ref>.
 
==Synonyms / Terminology==
 
None
 
==Epidemiology / Prevalence==
 
Accounts for 0.7-1.8% of AML, occurring in both children (median age of 13 years) and adults (median age of 35-44 years)<ref name=":0" />.
 
==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)
 
EXAMPLE Fatigue
 
EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
 
EXAMPLE Lymphocytosis (low level)
|}
 
 
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
 
Usually presents with anemia and thrombocytopenia and often with pancytopenia.  In adults, the median white blood cell count is 12x10^9/L, which is generally lower than other AML types<ref name=":0" />.
 
</blockquote>
==Sites of Involvement==
 
Bone marrow
 
==Morphologic Features==
 
This AML subtype may present with or without monocytic features and is frequently associated with basophilia (44-62% of cases) and multilineage dysplasia (most commonly granulocytic and erythroid, and less often megakaryocytic dysplasia)<ref name=":0" />.  Auer rods occur in ~1/3 of cases and ringed sideroblasts may also occur<ref name=":0" />.  The peripheral blood or bone marrow have >20% blasts characterized by a non-specific myeloid immunophenotype<ref name=":0" />.
 
==Immunophenotype==
 
The characteristic immunophenotype of the blasts associated with this entity is listed in the table below.  In addition, basophils may present as separate clusters of CD123+, CD33+ CD38+ and HLA-DR- cells<ref name=":0" />.
 
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
|Book
|Haematolymphoid Tumours (5th ed.)
|-
|-
|Positive (universal)||Myeloperoxidase (MPO), CD9, CD13, CD33, CD38 CD123, and HLA-DR
|Category
|Myeloid proliferations and neoplasms
|-
|-
|Positive (subset)||KIT(CD117), CD34, CD15, CD64 (monocyte-associated marker), and Dexoynucleotidyl Transferase (TdT)
|Family
|Acute myeloid leukaemia
|-
|-
|Negative (universal)||
|Type
|Acute myeloid leukaemia with defining genetic abnormalities
|-
|-
|Negative (subset)||
|Subtype(s)
|Acute myeloid leukaemia with DEK::NUP214 fusion
|}
|}


==Chromosomal Rearrangements (Gene Fusions)==
==Related Terminology==


Put your text here and fill in the table
{| class="wikitable"
 
|+
{| class="wikitable sortable"
|Acceptable
|Acute myeloid leukaemia with t(6;9)(p22.3;q34.1)
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|Not Recommended
!Diagnostic Significance (Yes, No or Unknown)
|N/A
!Prognostic Significance (Yes, No or Unknown)
|}
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|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).
==Gene Rearrangements==
|}
[[File:T(6;9)(p23;q34).png]]
 
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
 
This AML subtype is classified based on the presence of a t(6;9)(p23;q34.1), which results in fusion of the 5’ portion of ''DEK'' at “6p23” (specifically 6p22.3[hg38]) and the 3’ portion of ''NUP214''(''CAN'') at “9q34.1” (specifically 9q34.13[hg38]).  The breakpoints are intronic, producing an in-frame fusion<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=van Baal|first3=S.|last4=Jaegle|first4=M.|last5=de Wit|first5=T.|last6=Buijs|first6=A.|last7=Grosveld|first7=G.|date=1992|title=The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA|url=https://www.ncbi.nlm.nih.gov/pubmed/1549122|journal=Molecular and Cellular Biology|volume=12|issue=4|pages=1687–1697|doi=10.1128/mcb.12.4.1687|issn=0270-7306|pmc=PMC369612|pmid=1549122}}</ref>.  The ''DEK''-''NUP214'' fusion present on the derivative chromosome 6 is considered the pathogenic entity as the reciprocal ''NUP214''-''DEK'' fusion on chromosome 9 does not appear to be transcribed<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=Soekarman|first3=N.|last4=van Baal|first4=S.|last5=Jaegle|first5=M.|last6=Hagemeijer|first6=A.|last7=Bootsma|first7=D.|last8=Grosveld|first8=G.|date=1992|title=Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene|url=https://www.ncbi.nlm.nih.gov/pubmed/1308167|journal=Bailliere's Clinical Haematology|volume=5|issue=4|pages=857–879|doi=10.1016/s0950-3536(11)80049-1|issn=0950-3536|pmid=1308167}}</ref>.  Typically the ''DEK''-''NUP214'' fusion presents as the sole abnormality but can be part of a complex karyotype<ref name=":0" />.


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
|-
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
|t(6;9)(p23;q34.1)||5'DEK / 3'NUP214(CAN)||der(6)||0.7-1.8% of AML
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|''DEK''
|''DEK::NUP214''||The pathogenic derivative is the der(6) resulting in fusion of the proto-oncogene 5’ ''DEK'' and 3’''NUP214''(''CAN'').||t(6;9)(p23;q34.1)
|Rare (AML)
|D, P
|Yes (WHO)
|
*This AML subtype is classified based on the presence of a t(6;9)(p23;q34.1), which results in fusion of the 5’ portion of ''DEK'' at “6p23” (specifically 6p22.3[hg38]) and the 3’ portion of ''NUP214''(''CAN'') at “9q34.1” (specifically 9q34.13[hg38])<ref name=":0">WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024.  Online at: [https://tumourclassification.iarc.who.int/welcome/ WHO Classification of Tumours].</ref><ref>{{Cite journal|last=Khoury|first=Joseph D.|last2=Solary|first2=Eric|last3=Abla|first3=Oussama|last4=Akkari|first4=Yassmine|last5=Alaggio|first5=Rita|last6=Apperley|first6=Jane F.|last7=Bejar|first7=Rafael|last8=Berti|first8=Emilio|last9=Busque|first9=Lambert|date=2022-07|title=The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/35732831|journal=Leukemia|volume=36|issue=7|pages=1703–1719|doi=10.1038/s41375-022-01613-1|issn=1476-5551|pmc=9252913|pmid=35732831}}</ref>. The breakpoints are intronic, producing an in-frame fusion<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=van Baal|first3=S.|last4=Jaegle|first4=M.|last5=de Wit|first5=T.|last6=Buijs|first6=A.|last7=Grosveld|first7=G.|date=1992|title=The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA|url=https://www.ncbi.nlm.nih.gov/pubmed/1549122|journal=Molecular and Cellular Biology|volume=12|issue=4|pages=1687–1697|doi=10.1128/mcb.12.4.1687|issn=0270-7306|pmc=PMC369612|pmid=1549122}}</ref>. The ''DEK''-''NUP214'' fusion present on the derivative chromosome 6 is considered the pathogenic entity as the reciprocal ''NUP214''-''DEK'' fusion on chromosome 9 does not appear to be transcribed<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=Soekarman|first3=N.|last4=van Baal|first4=S.|last5=Jaegle|first5=M.|last6=Hagemeijer|first6=A.|last7=Bootsma|first7=D.|last8=Grosveld|first8=G.|date=1992|title=Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene|url=https://www.ncbi.nlm.nih.gov/pubmed/1308167|journal=Bailliere's Clinical Haematology|volume=5|issue=4|pages=857–879|doi=10.1016/s0950-3536(11)80049-1|issn=0950-3536|pmid=1308167}}</ref>.
*Typically, the ''DEK''-''NUP214'' fusion presents as the sole abnormality but can be part of a complex karyotype<ref name=":0" />.
*Cases with the 6;9 translocation and <20% blasts are not currently classified as AML, which is controversial. Such cases should have close follow-up to monitor for development of more definitive evidence of AML or may be treated as AML if clinically appropriate<ref name=":0" />.
*The t(6;9) occurs in 0.6-1.7% of AML cases in children<ref name=":1" /> (REFERENCES) and about 1% of adult AML cases (REFERENCES).
*''DEK''::''NUP214'' has traditionally been associated with a poor prognosis in both adult and pediatric AML cases<ref name=":0" />.  Of note, a 2014 retrospective analysis suggests a better outcome for pediatric patients with this translocation than previously reported<ref name=":1">{{Cite journal|last=Sandahl|first=Julie Damgaard|last2=Coenen|first2=Eva A.|last3=Forestier|first3=Erik|last4=Harbott|first4=Jochen|last5=Johansson|first5=Bertil|last6=Kerndrup|first6=Gitte|last7=Adachi|first7=Souichi|last8=Auvrignon|first8=Anne|last9=Beverloo|first9=H. Berna|date=2014|title=t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients|url=https://www.ncbi.nlm.nih.gov/pubmed/24441146|journal=Haematologica|volume=99|issue=5|pages=865–872|doi=10.3324/haematol.2013.098517|issn=1592-8721|pmc=4008104|pmid=24441146}}</ref>.  Elevated white blood cell counts and higher bone marrow blast percentages are associated with shorter periods of overall survival and disease-free survival, respectively<ref name=":0" />. Limited data suggests early allogeneic stem cell transplantation may be associated with better overall survival compared to patients without transplantation, suggesting accurate diagnosis for these patients is crucial<ref name=":0" /><ref>{{Cite journal|last=Slovak|first=M. L.|last2=Gundacker|first2=H.|last3=Bloomfield|first3=C. D.|last4=Dewald|first4=G.|last5=Appelbaum|first5=F. R.|last6=Larson|first6=R. A.|last7=Tallman|first7=M. S.|last8=Bennett|first8=J. M.|last9=Stirewalt|first9=D. L.|date=2006|title=A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare 'poor prognosis' myeloid malignancies|url=https://www.ncbi.nlm.nih.gov/pubmed/16628187|journal=Leukemia|volume=20|issue=7|pages=1295–1297|doi=10.1038/sj.leu.2404233|issn=0887-6924|pmid=16628187}}</ref><ref>{{Cite journal|last=Ishiyama|first=K.|last2=Takami|first2=A.|last3=Kanda|first3=Y.|last4=Nakao|first4=S.|last5=Hidaka|first5=M.|last6=Maeda|first6=T.|last7=Naoe|first7=T.|last8=Taniguchi|first8=S.|last9=Kawa|first9=K.|date=2012|title=Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/21869835|journal=Leukemia|volume=26|issue=3|pages=461–464|doi=10.1038/leu.2011.229|issn=1476-5551|pmid=21869835}}</ref>.
*The concurrent presence of FLT3-ITD does not appear to negatively impact survival in the pediatric population<ref name=":0" />.
|}
|}
 
==Individual Region Genomic Gain/Loss/LOH==
</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:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
 
This translocation has traditionally been associated with a poor prognosis in both adult and pediatric cases<ref name=":0" />.  Of note, a 2014 retrospective analysis suggests a better outcome for pediatric patients with this translocation than previously reported<ref>{{Cite journal|last=Sandahl|first=Julie Damgaard|last2=Coenen|first2=Eva A.|last3=Forestier|first3=Erik|last4=Harbott|first4=Jochen|last5=Johansson|first5=Bertil|last6=Kerndrup|first6=Gitte|last7=Adachi|first7=Souichi|last8=Auvrignon|first8=Anne|last9=Beverloo|first9=H. Berna|date=2014|title=t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients|url=https://www.ncbi.nlm.nih.gov/pubmed/24441146|journal=Haematologica|volume=99|issue=5|pages=865–872|doi=10.3324/haematol.2013.098517|issn=1592-8721|pmc=4008104|pmid=24441146}}</ref>.  Elevated white blood cell counts and higher bone marrow blast percentages are associated with shorter periods of overall survival and disease-free survival, respectively<ref name=":0" />.
 
Limited data suggests early allogeneic stem cell transplantation may be associated with better overall survival compared to patients without transplantation, suggesting accurate diagnosis for these patients is crucial<ref name=":0" /><ref>{{Cite journal|last=Slovak|first=M. L.|last2=Gundacker|first2=H.|last3=Bloomfield|first3=C. D.|last4=Dewald|first4=G.|last5=Appelbaum|first5=F. R.|last6=Larson|first6=R. A.|last7=Tallman|first7=M. S.|last8=Bennett|first8=J. M.|last9=Stirewalt|first9=D. L.|date=2006|title=A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare 'poor prognosis' myeloid malignancies|url=https://www.ncbi.nlm.nih.gov/pubmed/16628187|journal=Leukemia|volume=20|issue=7|pages=1295–1297|doi=10.1038/sj.leu.2404233|issn=0887-6924|pmid=16628187}}</ref><ref>{{Cite journal|last=Ishiyama|first=K.|last2=Takami|first2=A.|last3=Kanda|first3=Y.|last4=Nakao|first4=S.|last5=Hidaka|first5=M.|last6=Maeda|first6=T.|last7=Naoe|first7=T.|last8=Taniguchi|first8=S.|last9=Kawa|first9=K.|date=2012|title=Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/21869835|journal=Leukemia|volume=26|issue=3|pages=461–464|doi=10.1038/leu.2011.229|issn=1476-5551|pmid=21869835}}</ref>.
 
The concurrent presence of FLT3-ITD does not appear to negatively impact survival in the pediatric population<ref name=":0" />.
 
Cases with the 6;9 translocation and <20% blasts are not currently classified as AML, which is controversial.  Such cases should have close follow-up to monitor for development of more definitive evidence of AML or may be treated as AML if clinically appropriate<ref name=":0" />.
 
</blockquote>
==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>


{| 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
|N/A
 
|
7
|
|EXAMPLE Loss
|
|EXAMPLE
|
 
|
chr7:1- 159,335,973 [hg38]
|
|EXAMPLE
 
chr7
|Yes
|Yes
|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 reference).
|-
|EXAMPLE
 
8
|EXAMPLE Gain
|EXAMPLE
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
 
chr8
|No
|No
|No
|EXAMPLE
 
Common recurrent secondary finding for t(8;21) (add reference).
|}
|}
 
==Characteristic Chromosomal or Other Global Mutational Patterns==
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
 
Not applicable
</blockquote>
==Characteristic Chromosomal 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>


{| 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
|N/A
 
|
Co-deletion of 1p and 18q
|
|Yes
|No
|No
|EXAMPLE:
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
 
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
 
Not applicable
 
</blockquote>
==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>
 
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations
 
EXAMPLE:
 
EGFR; Exon 20 mutations
 
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
 
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<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.
==Gene Mutations (SNV/INDEL)==
 


<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
*COSMIC does not have specific information on mutations related to this subtype of AML.


COSMIC does not have specific information on mutations related to this subtype of AML.
===Other Mutations===
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Type!!Gene/Region/Other
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
|-
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
|Concomitant Mutations||FLT3-ITD (69% of children and 78% of adults)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
|-
!Established Clinical Significance Per Guidelines - Yes or No (Source)
|Secondary Mutations||
!Clinical Relevance Details/Other Notes
|-
|-
|Mutually Exclusive||FLT3-TKD is very uncommon
|''FLT3''
|}


</blockquote>
<br />
|ITD mutations
|Oncogene
|Common (AML with DEK::NUP214 fusion)
|<span class="blue-text">EXAMPLE:</span> T
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)
|
*FLT3-ITD occurs in 69% of children and 78% of adults.
*In contrast to FLT3-ITD mutations, FLT3-TKD is very uncommon.
*The concurrent presence of FLT3-ITD with t(6;9) does not appear to negatively impact survival in the pediatric population<ref name=":0" />.
|}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.
==Epigenomic Alterations==
==Epigenomic Alterations==


Line 273: Line 129:


==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>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|''DEK::NUP214''
|EXAMPLE: MAPK signaling
|Unknown
|EXAMPLE: Increased cell growth and proliferation
|The fusion protein is known to act as an aberrant transcription factor, alter nuclear transport and induce myeloid cell-specific global protein synthesis<ref name=":0" /><ref>{{Cite journal|last=Ageberg|first=Malin|last2=Drott|first2=Kristina|last3=Olofsson|first3=Tor|last4=Gullberg|first4=Urban|last5=Lindmark|first5=Anders|date=2008|title=Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis|url=https://www.ncbi.nlm.nih.gov/pubmed/18181180|journal=Genes, Chromosomes & Cancer|volume=47|issue=4|pages=276–287|doi=10.1002/gcc.20531|issn=1098-2264|pmid=18181180}}</ref>.
|-
|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
|}
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
The molecular mechanism is not completely understood, but the fusion protein is known to act as an aberrant transcription factor, alter nuclear transport and induce myeloid cell-specific global protein synthesis<ref name=":0" /><ref>{{Cite journal|last=Ageberg|first=Malin|last2=Drott|first2=Kristina|last3=Olofsson|first3=Tor|last4=Gullberg|first4=Urban|last5=Lindmark|first5=Anders|date=2008|title=Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis|url=https://www.ncbi.nlm.nih.gov/pubmed/18181180|journal=Genes, Chromosomes & Cancer|volume=47|issue=4|pages=276–287|doi=10.1002/gcc.20531|issn=1098-2264|pmid=18181180}}</ref>.
</blockquote>
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Karyotype, FISH, RT-PCR
Karyotype, FISH, RT-PCR (and any other fusion detecting technologies)


==Familial Forms==
==Familial Forms==
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==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 />
<references />
 
==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 [[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.


'''
Prior Author(s): 


==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>''Citation of this Page'': “Acute myeloid leukaemia with DEK::NUP214 fusion”. 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_DEK::NUP214_fusion</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with DEK::NUP214 fusion”. 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_DEK::NUP214_fusion</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases A]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases A]]
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