Biallelic inactivation of BRCA2 in Fanconi anemia

Niall G. Howlett, Toshiyasu Taniguchi, Susan Olson, Barbara Cox, Quinten Waisfisz, Christine De Die-Smulders, Nicole Persky, Markus Grompe, Hans Joenje, Gerard Pals, Hideyuki Ikeda, Edward A. Fox, Alan D. D'Andrea

Research output: Contribution to journalArticle

891 Scopus citations

Abstract

Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA I or BRCA2 mutations.

Original languageEnglish (US)
Pages (from-to)606-609
Number of pages4
JournalScience
Volume297
Issue number5581
DOIs
StatePublished - Jul 26 2002

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    Howlett, N. G., Taniguchi, T., Olson, S., Cox, B., Waisfisz, Q., De Die-Smulders, C., Persky, N., Grompe, M., Joenje, H., Pals, G., Ikeda, H., Fox, E. A., & D'Andrea, A. D. (2002). Biallelic inactivation of BRCA2 in Fanconi anemia. Science, 297(5581), 606-609. https://doi.org/10.1126/science.1073834