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: 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
• Journal: Science (New York, N.Y.) (Science) Vol. 297 Issue 5581 Pg. 606-9 (Jul 26 2002) ISSN: 1095-9203 [Electronic] United States
• PMID: 12065746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Alleles
• Amino Acid Sequence
• BRCA2 Protein (chemistry, genetics, 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, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection