Difference between revisions of "CEBPA"

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search
[unchecked revision][unchecked revision]
 
(43 intermediate revisions by 4 users not shown)
Line 1: Line 1:
 
==Primary Author(s)*==
 
==Primary Author(s)*==
  
Gordana Raca, MD, PhD, FACMG
+
Gordana Raca, MD, PhD, FACMG and Brian Davis PhD
 +
 
 
__TOC__
 
__TOC__
  
Line 9: Line 10:
 
CCAAT/Enhancer Binding Protein (C/EBP) Alpha;   
 
CCAAT/Enhancer Binding Protein (C/EBP) Alpha;   
 
CEBP;   
 
CEBP;   
C/EBP-Alpha
+
C/EBP-Alpha
 
 
EXAMPLE: Tumor protein p53, ''LFS1, p53, BCC7, TRP53''
 
  
 
==Genomic Location==
 
==Genomic Location==
 
   
 
   
'''Cytoband: 19q13.11 EXAMPLE: 17p13.1
+
'''Cytoband: 19q13.11
 
   
 
   
 
'''Genomic Coordinates:'''  
 
'''Genomic Coordinates:'''  
 +
 +
chr19:33,299,934-33,302,564(GRCh38/hg38)
  
 
chr19:33,790,840-33,793,430 [hg19]
 
chr19:33,790,840-33,793,430 [hg19]
  
EXAMPLE: chr17:7,571,720-7,590,868 [hg19]
+
==Cancer Category/Type==
  
EXAMPLE: chr17:7,668,402-7,687,538 [hg38]
+
[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.
  
==Cancer Category/Type==
 
  
Acute myeloid leukemia
+
*'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_Predisposition Myeloid Neoplasms with Germline Predisposition]'''
 +
 
 +
--- '''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_CEBPA_Mutation Myeloid Neoplasms with Germline CEBPA Mutation]'''
  
 
==Gene Overview==
 
==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).
+
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) [3].
  
 
==Common Alteration Types==
 
==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.  
+
* Bi-allelic ''CEBPA'' mutations define a specific entity in the 2016 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.  
+
* 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.  
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.  
+
* 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.  
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.  
+
 
 +
* 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% [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.  
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 46: Line 53:
 
! 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==
  
Put your text here
+
'''[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_CEBPA_mutation Acute Myeloid Leukemia (AML) with Biallelic Mutations of CEBPA]'''
+
 
EXAMPLE [[Germline Cancer Predisposition Genes]]
+
'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_CEBPA_Mutation Myeloid Neoplasms with Germline CEBPA Mutation]'''
  
 
==External Links==
 
==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.
+
'''[http://atlasgeneticsoncology.org//Genes/CEBPAID40050ch19q13.html ''CEBPA'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
 
 
EXAMPLES
 
 
 
'''[http://atlasgeneticsoncology.org/Genes/P53ID88.html ''TP53'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
 
 
 
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP53 ''TP53'' by COSMIC]''' - sequence information, expression, catalogue of mutations
 
  
'''[https://civicdb.org/events/genes/45/summary/variants/1300/summary ''TP53'' by CIViC]''' - general knowledge and evidence-based variant specific information
+
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=CEBPA ''CEBPA'' by COSMIC]''' - sequence information, expression, catalogue of mutations
  
'''[http://p53.iarc.fr/ ''TP53'' by IARC]''' - ''TP53'' database with reference sequences and mutational landscape
+
'''[https://civicdb.org/events/genes/15/summary/variants/594/summary/evidence/1512/summary#evidence ''CEBPA'' by CIViC]''' - general knowledge and evidence-based variant specific information
  
'''[https://pecan.stjude.cloud/proteinpaint/tp53 ''TP53'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.  
+
'''[https://pecan.stjude.cloud/proteinpaint/cebpa ''CEBPA'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.  
  
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=tp53 ''TP53'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
+
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=cebpa ''CEBPA'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
  
'''[http://www.cancerindex.org/geneweb/TP53.htm ''TP53'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
+
'''[http://www.cancerindex.org/geneweb/CEBPA.htm ''CEBPA'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
  
'''[http://oncokb.org/#/gene/TP53 ''TP53'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
+
'''[http://oncokb.org/#/gene/cebpa ''CEBPA'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
  
'''[https://www.mycancergenome.org/content/gene/tp53/ ''TP53'' by My Cancer Genome]''' - brief gene overview
+
'''[https://www.mycancergenome.org/content/gene/cebpa/ ''CEBPA'' by My Cancer Genome]''' - brief gene overview
  
'''[http://www.uniprot.org/uniprot/P04637 ''TP53'' by UniProt]''' - protein and molecular structure and function
+
'''[http://www.uniprot.org/uniprot/P49715 ''CEBPA'' by UniProt]''' - protein and molecular structure and function
  
'''[https://pfam.xfam.org/family/p53 ''TP53'' by Pfam]''' - gene and protein structure and function information
+
'''[http://pfam.xfam.org/protein/P49715 ''CEBPA'' by Pfam]''' - gene and protein structure and function information
  
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 ''TP53'' by GeneCards]''' - general gene information and summaries
+
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=cebpa ''CEBPA'' by GeneCards]''' - general gene information and summaries
  
'''[https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews]''' - information on Li Fraumeni Syndrome
+
'''[https://www.ncbi.nlm.nih.gov/gene/1050 ''CEBPA'' by NCBI Gene]''' - general gene information and summaries
  
 
==References==
 
==References==
  
=== EXAMPLE Book ===
+
1. Swerdlow SH 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, Volume 2, IARC Press: Lyon 2017, p. 142-144, p. 124-126.
  
Swerdlow SH 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, Volume 2, IARC Press: Lyon 2017, p. 142-144, p. 124-126
+
2. Tawana K, et al., (2015) Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood 126(10):1214-23, PMID 26162409.
  
=== EXAMPLE Journal Article ===
+
3. Avellino R.and Delwel R. (2017). Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation. Blood 129: 2083-2091.  PMID 28179278 DOI: 10.1182/blood-2016-09-687822
#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 ==
 
== 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>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:Cancer Genes C]]

Latest revision as of 13:53, 12 December 2023

Primary Author(s)*

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

Synonyms

CCAAT/Enhancer Binding Protein Alpha; CCAAT/Enhancer Binding Protein (C/EBP) Alpha; CEBP; C/EBP-Alpha

Genomic Location

Cytoband: 19q13.11

Genomic Coordinates:

chr19:33,299,934-33,302,564(GRCh38/hg38)

chr19:33,790,840-33,793,430 [hg19]

Cancer Category/Type

Acute Myeloid Leukemia (AML) with Biallelic Mutations of CEBPA - see Common Mutation Types below for more information.


--- Myeloid Neoplasms with Germline CEBPA Mutation

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) [3].

Common Alteration Types

  • Bi-allelic CEBPA mutations define a specific entity in the 2016 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% [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.
Copy Number Loss Copy Number Gain LOH Loss-of-Function Mutation Gain-of-Function Mutation Translocation/Fusion
X

Internal Pages

Acute Myeloid Leukemia (AML) with Biallelic Mutations of CEBPA

Myeloid Neoplasms with Germline CEBPA Mutation

External Links

CEBPA by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

CEBPA by COSMIC - sequence information, expression, catalogue of mutations

CEBPA by CIViC - general knowledge and evidence-based variant specific information

CEBPA by St. Jude ProteinPaint mutational landscape and matched expression data.

CEBPA by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

CEBPA by Cancer Index - gene, pathway, publication information matched to cancer type

CEBPA by OncoKB - mutational landscape, mutation effect, variant classification

CEBPA by My Cancer Genome - brief gene overview

CEBPA by UniProt - protein and molecular structure and function

CEBPA by Pfam - gene and protein structure and function information

CEBPA by GeneCards - general gene information and summaries

CEBPA by NCBI Gene - general gene information and summaries

References

1. Swerdlow SH 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, Volume 2, IARC Press: Lyon 2017, p. 142-144, p. 124-126.

2. Tawana K, et al., (2015) Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood 126(10):1214-23, PMID 26162409.

3. Avellino R.and Delwel R. (2017). Expression and regulation of C/EBPα in normal myelopoiesis and in malignant transformation. Blood 129: 2083-2091. PMID 28179278 DOI: 10.1182/blood-2016-09-687822

Notes

*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.