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

doi:10.1126/science.1073834

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

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983 Scopus citations

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 language	English (US)
Pages (from-to)	606-609
Number of pages	4
Journal	Science
Volume	297
Issue number	5581
DOIs	https://doi.org/10.1126/science.1073834
State	Published - Jul 26 2002
Externally published	Yes

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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 BRCA I or BRCA2 mutations.",

author = "Howlett, {Niall G.} and Toshiyasu Taniguchi and Susan Olson and Barbara Cox and Quinten Waisfisz and {De Die-Smulders}, Christine and Nicole Persky and Markus Grompe and Hans Joenje and Gerard Pals and Hideyuki Ikeda and Fox, {Edward A.} and D'Andrea, {Alan D.}",

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TY - JOUR

T1 - Biallelic inactivation of BRCA2 in Fanconi anemia

AU - Howlett, Niall G.

AU - Taniguchi, Toshiyasu

AU - Olson, Susan

AU - Cox, Barbara

AU - Waisfisz, Quinten

AU - De Die-Smulders, Christine

AU - Persky, Nicole

AU - Grompe, Markus

AU - Joenje, Hans

AU - Pals, Gerard

AU - Ikeda, Hideyuki

AU - Fox, Edward A.

AU - D'Andrea, Alan D.

PY - 2002/7/26

Y1 - 2002/7/26

N2 - 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.

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-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.

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Biallelic inactivation of BRCA2 in Fanconi anemia

Abstract

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