Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia

Tischkowitz, M.D., Morgan, N.V., Grimwade, D., Eddy, C., Ball, S., Vorechovsky, I., Langabeer, S., Stoger, R., Hodgson, S.V. and Mathew, C.G. (2004) Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia Leukemia, 18, (3), pp. 420-425. (doi:10.1038/sj.leu.2403280).


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Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (P<0.0001). Sequencing FANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1038/sj.leu.2403280
ISSNs: 0887-6924 (print)
Keywords: human, metabolism, dna, down-regulation, dna-binding proteins, male, acute disease, gene deletion, fanconi anemia complementation group a protein, sequence deletion, adolescent, homozygote, gene expression regulation, exons, aged, risk, mutation, analysis, genes, genetics, adult, protein, anemia, female, proteins, research support, physiology, leukemia, myeloid, middle aged,'t, fanconi anemia, London, 80 and over, dna methylation, population, humans, gene silencing, neoplastic, promoter regions (genetics)
ePrint ID: 60322
Date :
Date Event
Date Deposited: 05 Sep 2008
Last Modified: 16 Apr 2017 17:33
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