HAEM5:Acute myeloid leukaemia with CEBPA mutation: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<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:Acute Myeloid Leukemia (AML) with Biallelic Mutations of CEBPA]].

<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). 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>

Paul Defazio, MSc, Monash Health

 

 

==Cancer Category / Type==

 

 

==Cancer Sub-Classification / Subtype==

 

 

==Definition / Description of Disease==

 

 

 

 

 

 

 

==Clinical Features==

 

 

 

 

 

 

 

 

 

 

 

 

 

 

|Positive (universal)||EXAMPLE CD1

|Positive (subset)||EXAMPLE CD2

|Negative (universal)||EXAMPLE CD3

|Negative (subset)||EXAMPLE CD4

==Chromosomal Rearrangements (Gene Fusions)==

 

{| class="wikitable sortable"

|-

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

 

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}

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

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 5%

|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%

|}

</blockquote>

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|-

 

 

 

|Yes

|No

 

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

 

|EXAMPLE

 

|EXAMPLE

 

|No

|No

|EXAMPLE

 

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

!Chromosome Number!!Gain/Loss/Amp/LOH!!Region

|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000

|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000

</blockquote>

 

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"

|-

|EXAMPLE

 

|Yes

|No

|No

|EXAMPLE:

 

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>

!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

 

 

 

|}

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.}}

{| class="wikitable sortable"

!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)

|''CEBPA''||c.939_940insAAG, p.K313_V314insK||Oncogene||LOF||52

|''CEBPA''||c.68_69insC, p.H24fs*84||Oncogene||LOF||43

|''CEBPA''||c.247delC, p.Q83fs*77||Oncogene||LOF||32

|-

|''CEBPA''||c.936_937insCAG, p.Q312_K313insQ||Oncogene||LOF||28

|''CEBPA''||c.912_913insTTG, p.K304_Q305insL||Oncogene||LOF||24

===Other Mutations===

Concurrent mutations in ''NPM1'' and ''FLT3'' are seen less frequently in individuals with biallelic ''CEBPA'' mutations than in those with no or monoallelic mutations<ref name=":2" />. Conversely, mutations in ''GATA2'' appear to occur more often in ''CEBPA'' single- and double-mutants<ref>{{Cite journal|last=Green|first=Claire L.|last2=Tawana|first2=Kiran|last3=Hills|first3=Robert K.|last4=Bödör|first4=Csaba|last5=Fitzgibbon|first5=Jude|last6=Inglott|first6=Sarah|last7=Ancliff|first7=Phil|last8=Burnett|first8=Alan K.|last9=Linch|first9=David C.|date=2013|title=GATA2 mutations in sporadic and familial acute myeloid leukaemia patients with CEBPA mutations|url=https://www.ncbi.nlm.nih.gov/pubmed/23560626|journal=British Journal of Haematology|volume=161|issue=5|pages=701–705|doi=10.1111/bjh.12317|issn=1365-2141|pmid=23560626}}</ref>. The prognostic significance of these concomitant mutations is, however, unclear. Biallelic ''CEBPA'' mutations appear to confer a positive prognostic effect regardless of concomitant mutations.

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

Familial mutations of ''CEBPA'' have been described in several families<ref name=":3" /><ref>{{Cite journal|last=Nanri|first=Tomoko|last2=Uike|first2=Naokuni|last3=Kawakita|first3=Toshiro|last4=Iwanaga|first4=Eisaku|last5=Mitsuya|first5=Hiroaki|last6=Asou|first6=Norio|date=2010|title=A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/19953636|journal=Genes, Chromosomes & Cancer|volume=49|issue=3|pages=237–241|doi=10.1002/gcc.20734|issn=1098-2264|pmid=19953636}}</ref><ref>{{Cite journal|last=Sellick|first=G. S.|last2=Spendlove|first2=H. E.|last3=Catovsky|first3=D.|last4=Pritchard-Jones|first4=K.|last5=Houlston|first5=R. S.|date=2005|title=Further evidence that germline CEBPA mutations cause dominant inheritance of acute myeloid leukaemia|url=https://www.ncbi.nlm.nih.gov/pubmed/15902292|journal=Leukemia|volume=19|issue=7|pages=1276–1278|doi=10.1038/sj.leu.2403788|issn=0887-6924|pmid=15902292}}</ref>. Typically, these are N-terminal mutations that are later joined by a somatic C-terminal mutation on the opposite allele leading to AML.

(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 />

<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.

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