EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer

被引：344

作者：

Hughes-Davies, L

Huntsman, D

Ruas, M

Fuks, F

Bye, J

Chin, SF

Milner, J

Brown, LA

Hsu, F

Gilks, B

Nielsen, T

Schulzer, M

Chia, S

Ragaz, J

Cahn, A

Linger, L

Ozdag, H

Cattaneo, E

Jordanova, ES

Schuuring, E

Yu, DS

Venkitaraman, A

Ponder, B

Doherty, A

Aparicio, S

Bentley, D

Theillet, C

Ponting, CP

Caldas, C

Kouzarides, T

机构：

[1] Canc Res UK, Wellcome Trust Inst, Cambridge CB2 1QR, England

[2] Canc Res UK, Dept Pathol, Cambridge CB2 1QR, England

[3] Univ Cambridge, Dept Oncol, MRC, Res Ctr, Cambridge CB2 2XZ, England

[4] Vancouver Gen Hosp, Dept Pathol, Genet Pathol Evaluat Ctr, Vancouver, BC V6H 3Z6, Canada

[5] Vancouver Gen Hosp, Prostate Ctr, Vancouver, BC V6H 3Z6, Canada

[6] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V6H 3Z6, Canada

[7] Univ British Columbia, Vancouver, BC V6H 3Z6, Canada

[8] Wellcome Trust Sanger Inst Hinxton, Cambridge CB10 1SA, England

[9] Univ British Columbia, Dept Stat & Med, Vancouver, BC V6T 2B5, Canada

[10] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada

[11] Leiden Univ, Ctr Med, Dept Pathol, NL-2300 RC Leiden, Netherlands

[12] Univ Groningen Hosp, Dept Pathol, NL-9700 RB Groningen, Netherlands

[13] MRC, Canc Cell Unit, Res Ctr, Cambridge CB2 2XZ, England

[14] Cambridge Inst Med Res, Cambridge CB2 2XZ, England

[15] Ctr Val Aurelle, INSERM, EMI 229, Montpellier, France

[16] Univ Oxford, MRC, Funct Genet Unit, Oxford OX1 3QX, England

来源：

CELL | 2003年 / 115卷 / 05期

关键词：

D O I：

10.1016/S0092-8674(03)00930-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1beta and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

引用

页码：523 / 535

页数：13

共 40 条

[1] The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif [J].