title: Biallelic inactivation of BRCA2 in Fanconi anemia.
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 BRCA1 or BRCA2 mutations.
authors.affiliation: Department of Pediatric Oncology, Children's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Niall G
authors.initials: NG
authors.lastname: Howlett
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Susan
authors.initials: S
authors.lastname: Olson
authors.forename: Barbara
authors.initials: B
authors.lastname: Cox
authors.forename: Quinten
authors.initials: Q
authors.lastname: Waisfisz
authors.forename: Christine
authors.initials: C
authors.lastname: De Die-Smulders
authors.forename: Nicole
authors.initials: N
authors.lastname: Persky
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Hans
authors.initials: H
authors.lastname: Joenje
authors.forename: Gerard
authors.initials: G
authors.lastname: Pals
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fox
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D005347:Fibroblasts; D016368:Frameshift Mutation; D020868:Gene Silencing; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005816:Genetic Complementation Test; D018095:Germ-Line Mutation; D006720:Homozygote; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D024682:BRCA2 Protein; D020033:Protein Isoforms; D012333:RNA, Messenger; D016685:Mitomycin