CEBPA
Primary Author(s)*
Gordana Raca, MD, PhD, FACMG
Synonyms
CCAAT/Enhancer Binding Protein Alpha; CCAAT/Enhancer Binding Protein (C/EBP) Alpha; CEBP; C/EBP-Alpha
EXAMPLE: Tumor protein p53, LFS1, p53, BCC7, TRP53
Genomic Location
Cytoband: 19q13.11 EXAMPLE: 17p13.1
Genomic Coordinates:
chr19:33,790,840-33,793,430 [hg19]
EXAMPLE: chr17:7,571,720-7,590,868 [hg19]
EXAMPLE: chr17:7,668,402-7,687,538 [hg38]
Cancer Category/Type
Acute myeloid leukemia
Gene Overview
CEBPA is an intronless gene encoding a transcription factor that contains a basic leucine zipper (bZIP) domain and recognizes the CCAAT motif in the promoters of target genes. The CEBPA-encoded protein functions in homodimers and also heterodimers with CCAAT/enhancer-binding proteins beta and gamma to modulate the expression of genes involved in cell cycle regulation. It coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. It is essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP).
Common Alteration Types
Bi-allelic CEBPA mutations define a specific entity in the 2017 WHO classification of hematologic neoplasms [1]. AML cases with only one CEBPA mutation have different biologic and clinical characteristics and should not be classified into this category. AML with bi-allelic CEBPA mutations typically presents 'de novo'; it accounts for approximately 4-9% of AML cases in children and young adults, and appears to be less common in older patients. Morphologically it meets the criteria for AML with or without maturation and more rarely may show myelomonocitic or monoblastic features. There are no any distinctive morphologic or immunophenotypic characteristics. More than 70% of the cases have a normal karyotype. The remaining cases may show del(9q) or different non-specific chromosome abnormalities. 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%. 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.
| 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 |
Internal Pages
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External Links
Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.
EXAMPLES
TP53 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
TP53 by COSMIC - sequence information, expression, catalogue of mutations
TP53 by CIViC - general knowledge and evidence-based variant specific information
TP53 by IARC - TP53 database with reference sequences and mutational landscape
TP53 by St. Jude ProteinPaint mutational landscape and matched expression data.
TP53 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
TP53 by Cancer Index - gene, pathway, publication information matched to cancer type
TP53 by OncoKB - mutational landscape, mutation effect, variant classification
TP53 by My Cancer Genome - brief gene overview
TP53 by UniProt - protein and molecular structure and function
TP53 by Pfam - gene and protein structure and function information
TP53 by GeneCards - general gene information and summaries
GeneReviews - information on Li Fraumeni Syndrome
References
EXAMPLE Book
- Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
EXAMPLE Journal Article
- Li Y, et al., (2001). Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 28:220-221, PMID 11431691.
Notes
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