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

Research output: Contribution to journal › Article › peer-review

1021 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

Funding

Funders	Funder number
National Institute of Health National Heart, Lung, and Blood Institute	R01HL052725

ASJC Scopus subject areas

General

Access to Document

10.1126/science.1073834

Cite this

@article{202a6ceeaf154b0081227986d9d84267,

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.\}",

year = "2002",

month = jul,

day = "26",

doi = "10.1126/science.1073834",

language = "English (US)",

volume = "297",

pages = "606--609",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5581",

}

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.

UR - https://www.scopus.com/pages/publications/18444362122

UR - https://www.scopus.com/pages/publications/18444362122#tab=citedBy

U2 - 10.1126/science.1073834

DO - 10.1126/science.1073834

M3 - Article

C2 - 12065746

AN - SCOPUS:18444362122

SN - 0036-8075

VL - 297

SP - 606

EP - 609

JO - Science

JF - Science

IS - 5581

ER -

Biallelic inactivation of BRCA2 in Fanconi anemia

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this