Biallelic inactivation of BRCA2 in Fanconi anemia

被引：884

作者：

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

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA

[3] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA

[4] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA

[5] Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands

[6] Univ Limburg, Acad Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands

[7] Sapporo Med Univ, Sch Med, Dept Pathol, Chuo Ku, Sapporo, Hokkaido 0608557, Japan

来源：

SCIENCE | 2002年 / 297卷 / 5581期

关键词：

D O I：

10.1126/science.1073834

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：606 / 609

页数：5

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