Biallelic inactivation of BRCA2 in Fanconi anemia

Science. 2002 Jul 26;297(5581):606-9. doi: 10.1126/science.1073834. Epub 2002 Jun 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • BRCA2 Protein / chemistry
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism*
  • Cell Line
  • DNA Damage
  • Fanconi Anemia / genetics*
  • Female
  • Fibroblasts
  • Frameshift Mutation
  • Gene Silencing
  • Genes, BRCA1
  • Genes, BRCA2*
  • Genetic Complementation Test
  • Germ-Line Mutation
  • Homozygote
  • Humans
  • Male
  • Mitomycin / pharmacology
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Phenotype
  • Protein Isoforms
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • BRCA2 Protein
  • Protein Isoforms
  • RNA, Messenger
  • Mitomycin