Co-amplification of CCND1 and EMSY is associated with an adverse outcome in ER-positive tamoxifen-treated breast cancers

被引:31
作者
Brown, Lindsay A. [1 ]
Johnson, Karynn [1 ]
Leung, Samuel [2 ]
Bismar, Tarek A. [3 ]
Benitez, Javier [5 ]
Foulkes, William D. [4 ]
Huntsman, David G. [1 ]
机构
[1] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada
[2] British Columbia Canc Agcy, Genet Pathol Evaluat Ctr, Jack Bell Res Ctr, Vancouver, BC V6H 3Z6, Canada
[3] McGill Univ, Jewish Gen Hosp, Dept Pathol & Oncol, Montreal, PQ H2W 1S6, Canada
[4] McGill Univ, Program Canc Genet, Dept Oncol, Gerald Bronfman Ctr Canc Res, Montreal, PQ H2W 1S6, Canada
[5] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Madrid 28029, Spain
关键词
Gene amplification; Breast cancer; Tissue microarray; CELL-CYCLE PROGRESSION; BRCA1 PROMOTER REGION; SPORADIC BREAST; OVARIAN-CANCER; 11Q13; AMPLIFICATION; TISSUE MICROARRAY; PROGNOSTIC VALUE; TUMORS; D1; EXPRESSION;
D O I
10.1007/s10549-009-0479-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Amplification of chromosome 11q13 is commonly seen in breast carcinomas and candidate genes from this region include CCND1 and EMSY. Here, we investigate the prognostic significance of CCND1 and EMSY amplification in a large series of breast carcinomas and in BRCA1 and BRCA2 mutation positive breast cancers. Amplification of CCND1 and EMSY was assessed by fluorescent in situ hybridization. Both CCND1 and EMSY amplifications were associated with a significantly worse outcome in ER-positive patients treated with tamoxifen only, in contrast to nonamplified tumors (P = 8.55 x 10(-4) and P = 8.35 x 10(-5), respectively). In multivariable Cox models, which included standard prognostic markers, co-amplification of CCND1 and EMSY was significantly more predictive of outcome than was amplification of either gene alone or neither gene amplified in ER-positive tamoxifen-treated patients (P = 5.47 x 10(-5)). EMSY gene amplification was a significantly less common event in BRCA2 mutation carriers as compared to BRCA1 mutation carriers (9 versus 24%, respectively). In contrast, CCND1 amplification occurred at a similar frequency in both BRCA1 and BRCA2 breast cancers (22 versus 18%, respectively). In summary, co-amplification of CCND1 and EMSY identified a poor prognostic subset of ER-positive tamoxifen-treated patients. In addition, EMSY amplification occurred at a lower frequency in BRCA2 mutation carriers providing evidence to support EMSY amplification as a somatic surrogate for BRCA2 loss in sporadic breast cancer.
引用
收藏
页码:347 / 354
页数:8
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