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==Primary Author(s)*==
==Primary Author(s)*==
Kay Weng Choy MBBS
Kay Weng Choy, MBBS, Monash Medical Centre
__TOC__
__TOC__
chr3:128,479,422-128,493,187 (GRCh38/hg38)
chr3:128,479,422-128,493,187 (GRCh38/hg38)
chr3:128,198,265-128,212,030 (GRCh37/hg19)
chr3:128,198,265-128,212,030 (GRCh37/hg19)
==Cancer Category/Type==
==Cancer Category/Type==
Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), chronic myeloid leukemia (CML)
*'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_Predisposition Myeloid Neoplasms with Germline Predisposition]'''
--- '''[http://www.ccga.io/index.php/HAEM4:Myeloid_Neoplasms_with_Germline_GATA2_Mutation Myeloid Neoplasms with Germline GATA2 Mutation]'''
Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
Chronic myeloid leukemia (CML)
Non-small cell lung cancer (NSCLC)
Non-small cell lung cancer (NSCLC)
==Common Alteration Types==
==Common Alteration Types==
GATA2 mutations include amino acid substitutions, insertion and deletions, and frameshifts scattered throughout the gene but predominantly found in the region encoding the two zinc finger domains [1]. Approximately 100 GATA2 mutations have been described, either as germline genetic defects or somatic mutations in association with other drivers, such as biallelic CEBPA mutation in AML [1].
• About one-third of all germline mutations are inherited and the rest occur de novo; these include a small number of whole gene deletions and 29 frameshift or nonsense mutations, distributed from the initiation site to the end of the second zinc finger
• A further 11 in-frame insertions or deletions and 54 single nucleotide variants causing amino acid substitution are predominantly found in exons 3, 4 and 5, encoding the two zinc finger domains
• Splice site mutations are also found between coding exons 3 and 4
• Two discrete mutations of the intron 5 enhancer, predicted to affect transcription factor binding, have also been reported
• Overall, approximately two-thirds of all cases described have mutations in the zinc finger domains
• No mutations have been observed in the 5’ or 3’ untranslated regions (UTRs) or in the distal section of the last exon, beyond the region encoding the second zinc finger
• Many single amino acid substitutions are predicted to significantly impair DNA binding of the zinc fingers potentially making them functionally inactive. It is also possible that these variants have residual function or can even act in a dominant negative fashion
• Although more than half the variants described are single amino acid substitutions that may lead to the translation of mutated protein with altered function, it is proposed that the functional effects of heterozygous mutations are primarily due to haploinsufficiency
According to the Catalogue of Somatic Mutations in Cancer (COSMIC), c.490G>A (NM_032638.4) (p.Ala164Thr) and c.15C>G (NM_032638.4) (p.Pro5Pro) have been observed in 49 and 96 cases, respectively, predominantly in the setting of acute myeloid leukemia (https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=GATA2, Accessed 1st August 2018)
==Internal Pages==
==Internal Pages==
'''[[HAEM5:Acute myeloid leukaemia with MECOM rearrangement]]'''
'''[[HAEM4:Myeloid Neoplasms with Germline GATA2 Mutation]]'''
==External Links==
==External Links==
'''[http://atlasgeneticsoncology.org/Genes/GATA2ID44160ch3q21.html ''GATA2'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=GATA2 ''GATA2'' by COSMIC]''' - sequence information, expression, catalogue of mutations
'''[http://atlasgeneticsoncology.org/Genes/P53ID88.html ''TP53'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[https://civicdb.org/events/genes/25/summary/variants/57/summary ''GATA2'' by CIViC]''' - general knowledge and evidence-based variant specific information
'''[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP53 ''TP53'' by COSMIC]''' - sequence information, expression, catalogue of mutations
'''[https://pecan.stjude.cloud/proteinpaint/gata2 ''GATA2'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
'''[https://civicdb.org/events/genes/45/summary/variants/1300/summary ''TP53'' by CIViC]''' - general knowledge and evidence-based variant specific information
'''[https://pmkb.weill.cornell.edu/search?utf8=%E2%9C%93&search=gata2 ''GATA2'' by Precision Medicine Knowledgebase (Weill Cornell)]''' - manually vetted interpretations of variants and CNVs
'''[http://p53.iarc.fr/ ''TP53'' by IARC]''' - ''TP53'' database with reference sequences and mutational landscape
'''[http://www.cancerindex.org/geneweb/GATA2.htm ''GATA2'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[https://pecan.stjude.cloud/proteinpaint/tp53 ''TP53'' by St. Jude ProteinPaint]''' mutational landscape and matched expression data.
'''[http://oncokb.org/#/gene/gata2 ''GATA2'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
'''[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://www.ncbi.nlm.nih.gov/gene/2624 ''GATA2'' by NCBI Gene]''' - brief gene overview
'''[http://www.cancerindex.org/geneweb/TP53.htm ''TP53'' by Cancer Index]''' - gene, pathway, publication information matched to cancer type
'''[https://www.mycancergenome.org/content/gene/gata2/ ''GATA2'' by My Cancer Genome]''' - brief gene overview
'''[http://oncokb.org/#/gene/TP53 ''TP53'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
'''[http://www.uniprot.org/uniprot/P23769 ''GATA2'' by UniProt]''' - protein and molecular structure and function
'''[https://www.mycancergenome.org/content/gene/tp53/ ''TP53'' by My Cancer Genome]''' - brief gene overview
'''[https://pfam.xfam.org/protein/P23769 ''GATA2'' by Pfam]''' - gene and protein structure and function information
'''[http://www.uniprot.org/uniprot/P04637 ''TP53'' by UniProt]''' - protein and molecular structure and function
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=gata2 ''GATA2'' by GeneCards]''' - general gene information and summaries
'''[https://pfam.xfam.org/family/p53 ''TP53'' by Pfam]''' - gene and protein structure and function information
'''[http://www.omim.org/entry/137295 ''GATA2'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=tp53 ''TP53'' by GeneCards]''' - general gene information and summaries
'''[https://databases.lovd.nl/shared/genes/GATA2 ''GATA2'' by LOVD(3)]''' - Leiden Open Variation Database
'''[https://www.ncbi.nlm.nih.gov/books/NBK1311/ GeneReviews]''' - information on Li Fraumeni Syndrome
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=GATA2 ''GATA2'' by TICdb]''' - database of Translocation breakpoints In Cancer
==References==
==References==
1. Collin M, et al., (2015). Haematopoietic and immune defects associated with GATA2 mutation. Br J Haematol 169(2):173-187. PMID 25707267
2. Tsai FY, et al., (1994). An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371(6494):221-226. PMID 8078582
3. Doré LC, et al., (2012). Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis. Blood 119(16):3724-3733. PMID 22383799
4. May G, et al., (2013). Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors. Cell Stem Cell 13(6):754-768. PMID 24120743
5. Beck D, et al., (2013). Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes. Blood 122(14);e12-e22. PMID 23974199
6. Vicente C, et al., (2012). Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities. Leukemia 26(3):550-554. PMID 21904383
7. Ayala RM, et al., (2009). Clinical significance of Gata-1, Gata-2, EKLF, and c-MPL expression in acute myeloid leukemia. Am J Hematol 84(20:79-86. PMID 19097174
8. Spinner MA, et al., (2014). GATA2 deficiency: a protein disorder of hematopoiesis, lymphatics, and immunity. Blood 123(6):809-821. PMID 24227816
9. Gröschel S, et al., (2014). A single oncogenic enhancer rearrangement cause concomitant EVI1 and GATA2 reregulation in leukemia. Cell 157(20):369-381. PMID 24703711
10. Zhang SJ, et al., (2008). Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci U S A 105(6):2076-2081. PMID 18250304
11. Zhang SJ, et al., (2009). GATA-2 L359V mutation is exclusively associated with CML progression but no other haematological malignancies and GATA-2 P250A is a novel single nucleotide polymorphism. PMID 19304323
12. Kumar MS, et al., (2012). The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer. PMID 22541434
== 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 G]]
[[Category:Cancer Genes G]]