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

868 Citations (Scopus)

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
Externally publishedYes

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Fanconi Anemia
Mitomycin
Genes
BRCA2 Protein
BRCA2 Gene
BRCA1 Gene
Mutation
Germ-Line Mutation
Neoplasms
Hypersensitivity
Complementary DNA
Fibroblasts
Cell Line

ASJC Scopus subject areas

  • General

Cite this

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

Biallelic inactivation of BRCA2 in Fanconi anemia. / Howlett, Niall G.; Taniguchi, Toshiyasu; Olson, Susan; Cox, Barbara; Waisfisz, Quinten; De Die-Smulders, Christine; Persky, Nicole; Grompe, Markus; Joenje, Hans; Pals, Gerard; Ikeda, Hideyuki; Fox, Edward A.; D'Andrea, Alan D.

In: Science, Vol. 297, No. 5581, 26.07.2002, p. 606-609.

Research output: Contribution to journalArticle

Howlett, NG, Taniguchi, T, Olson, S, Cox, B, Waisfisz, Q, De Die-Smulders, C, Persky, N, Grompe, M, Joenje, H, Pals, G, Ikeda, H, Fox, EA & D'Andrea, AD 2002, 'Biallelic inactivation of BRCA2 in Fanconi anemia', Science, vol. 297, no. 5581, pp. 606-609. https://doi.org/10.1126/science.1073834
Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science. 2002 Jul 26;297(5581):606-609. https://doi.org/10.1126/science.1073834
Howlett, Niall G. ; Taniguchi, Toshiyasu ; Olson, Susan ; Cox, Barbara ; Waisfisz, Quinten ; De Die-Smulders, Christine ; Persky, Nicole ; Grompe, Markus ; Joenje, Hans ; Pals, Gerard ; Ikeda, Hideyuki ; Fox, Edward A. ; D'Andrea, Alan D. / Biallelic inactivation of BRCA2 in Fanconi anemia. In: Science. 2002 ; Vol. 297, No. 5581. pp. 606-609.
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AU - De Die-Smulders, Christine

AU - Persky, Nicole

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