RT Journal Article
SR Electronic
T1 Biallelic Inactivation of <em>BRCA2</em> in Fanconi Anemia
JF Science
JO Science
FD American Association for the Advancement of Science
SP 606
OP 609
DO 10.1126/science.1073834
VO 297
IS 5581
A1 Howlett, Niall G.
A1 Taniguchi, Toshiyasu
A1 Olson, Susan
A1 Cox, Barbara
A1 Waisfisz, Quinten
A1 de Die-Smulders, Christine
A1 Persky, Nicole
A1 Grompe, Markus
A1 Joenje, Hans
A1 Pals, Gerard
A1 Ikeda, Hideyuki
A1 Fox, Edward A.
A1 D'Andrea, Alan D.
YR 2002
UL http://science.sciencemag.org/content/297/5581/606.abstract
AB 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-typeBRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families withBRCA1 or BRCA2 mutations.