Changes

Gordana Raca, MD, PhD, FACMG and Brian Davis PhD

Gordana Raca, MD, PhD, FACMG and Brian Davis PhD

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==Cancer Category/Type==

==Cancer Category/Type==

Acute myeloid leukemia

[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_CEBPA_mutation Acute Myeloid Leukemia (AML) with Biallelic Mutations of CEBPA] - see Common Mutation Types below for more information.

 

 

 

==Gene Overview==

==Gene Overview==

* The bi-allelic ''CEBPA'' mutation is associated with a specific gene expression profile in leukemia clones, that is not seen in cases with a single ''CEBPA'' mutation. ''FLT3''-ITD mutation is observed in 5-9% of the cases, while ''GATA2'' zing-finger 1 mutation occurs in 39% of the patients. Importantly, all patients with bi-allelic ''CEBPA'' mutations have to be evaluted for the germline mutation status, to exclude germline inheritance of one of the alleles. Germline mutations in one copy of the ''CEBPA'' gene are associated with a familial AML syndrome which typically manifests as development of leukemia in childhood or adolescence (median age 24.5 years) in the absence of preceding abnormal blood counts or other clinical phenotypes. In AML with germline ''CEBPA'' mutation, the first mutation is germline and commonly occurs in the 5' end of the gene. The second mutation occurs as a somatic change in leukemia cells and typically localizes within the 3' end of the gene. The disorder appears to have near-complete penetrance for development of AML. AML with germline ''CEBPA'' mutation is associated with a favorable prognosis, with the survival rate reported in one study as 67% [2]. However, patients frequently experience recurrence, which at least in a subset of cases may in fact represent development of a novel independent clone with bi-allelic mutation rather than a true relapse.  

* The bi-allelic ''CEBPA'' mutation is associated with a specific gene expression profile in leukemia clones, that is not seen in cases with a single ''CEBPA'' mutation. ''FLT3''-ITD mutation is observed in 5-9% of the cases, while ''GATA2'' zing-finger 1 mutation occurs in 39% of the patients. Importantly, all patients with bi-allelic ''CEBPA'' mutations have to be evaluted for the germline mutation status, to exclude germline inheritance of one of the alleles. Germline mutations in one copy of the ''CEBPA'' gene are associated with a familial AML syndrome which typically manifests as development of leukemia in childhood or adolescence (median age 24.5 years) in the absence of preceding abnormal blood counts or other clinical phenotypes. In AML with germline ''CEBPA'' mutation, the first mutation is germline and commonly occurs in the 5' end of the gene. The second mutation occurs as a somatic change in leukemia cells and typically localizes within the 3' end of the gene. The disorder appears to have near-complete penetrance for development of AML. AML with germline ''CEBPA'' mutation is associated with a favorable prognosis, with the survival rate reported in one study as 67% [2]. However, patients frequently experience recurrence, which at least in a subset of cases may in fact represent development of a novel independent clone with bi-allelic mutation rather than a true relapse.  

Sporadic cases of AML with bi-allelic ''CEBPA'' mutations are also associated with a favorable prognosis, similar to that of inv(16) or t(8;21) AML. The influence of ''FLT3''-ITD and ''GATA2'' mutations on prognosis of AML with bi-allelic ''CEBPA'' mutations is presently unclear.  

 

* Sporadic cases of AML with bi-allelic ''CEBPA'' mutations are also associated with a favorable prognosis, similar to that of inv(16) or t(8;21) AML. The influence of ''FLT3''-ITD and ''GATA2'' mutations on prognosis of AML with bi-allelic ''CEBPA'' mutations is presently unclear.  

{| class="wikitable sortable"

{| class="wikitable sortable"

! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  

! Copy Number Loss  !! Copy Number Gain  !!  LOH  !!  Loss-of-Function Mutation  !!  Gain-of-Function Mutation  !!  Translocation/Fusion  

|-

|-

| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X

| ||  ||  || X || ||  

|}

|}

==Internal Pages==

==Internal Pages==

 

==External Links==

==External Links==