Amplification of 11q13 in ovarian carcinoma

被引:115
作者
Brown, Lindsay A. [1 ,2 ]
Kalloger, Steve E. [1 ,2 ,3 ]
Miller, Melinda A. [1 ,2 ]
Shih, le-Ming [4 ,5 ,6 ]
McKinney, Steven E. [7 ]
Santos, Jennifer L. [8 ,9 ,10 ]
Swenerton, Ken [11 ,12 ]
Spellman, Paul T. [13 ]
Gray, Joe [13 ]
Gilks, C. Blake [1 ,2 ]
Huntsman, David G. [1 ,2 ]
机构
[1] British Columbia Canc Agcy, Dept Pathol, Vancouver Coastal Hlth Res Inst, Genet Pathol Evaluat Ctr, Vancouver, BC V5Z 4E6, Canada
[2] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
[3] Vancouver Gen Hosp, Dept Anat Pathol, Vancouver, BC, Canada
[4] Johns Hopkins Univ, Sch Med, Dept Pathol Oncol & Gynecol & Obstet, Baltimore, MD USA
[5] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA
[7] British Columbia Canc Res Ctr, Mol Oncol & Breast Canc Program, Vancouver, BC V5Z 1L3, Canada
[8] Vancouver Gen Hosp, Dept Gynecol, Vancouver, BC, Canada
[9] British Columbia Canc Agcy, Cheryl Brown Ovarian Canc Outcomes Unit, Vancouver, BC V5Z 4E6, Canada
[10] British Columbia Canc Agcy, Dept Gynecol Oncol, Vancouver, BC V5Z 4E6, Canada
[11] Univ British Columbia, Dept Med, Vancouver, BC, Canada
[12] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada
[13] Univ Calif San Francisco, Lawrence Berkeley Natl Lab, Div Life Sci, San Francisco, CA 94143 USA
关键词
D O I
10.1002/gcc.20549
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Amplification at the 11q13 locus is commonly observed in breast, ovarian, head and neck, oral, and esophageal cancer. Studies of this region led to the identification of multiple amplicons containing several potential oncogenes including EMSY PAK1, RSF1, and GAB2. Here, we investigate the amplification of the above four genes and their prognostic significance in histologically and clinically defined subsets of ovarian cancer. Amplification of all four genes was assessed by fluorescent in situ hybridization in tissue microarrays containing 538 clinically annotated ovarian carcinomas with 12 years of follow-up data. Overall, for the entire cohort, EMSY was amplified in 44 (16%) of 269 cases, PAK1 was amplified in 38 (15%) of 255 cases, RSF1 was amplified in 37 (12%) of 310 cases, and GAB2 was amplified in 41 (16%) of 255 cases. Amplification of EMSY PAK1, RSF1, and GAB2 were all highly correlated with each other and with a serous histology. Univariate survival analysis showed that tumors with EMSY and RSF1 amplification were associated with a significantly worse outcome. A molecular inversion probe array was then used to study the 11q13 amplicon in 33 high grade serous carcinomas. The core of the amplicon mapped to a 6-Mb region encompassing EMSY, PAK1, RSF1, and GAB2. However, a second more telomeric amplicon was also observed for which no candidate genes have been identified. In summary, amplification of these four putative oncogenes from 11q13 in early ovarian cancer is associated with a serous histology and in the case of EMSY and RSF1 a poor outcome. These findings support the hypothesis that the 11q13 amplicon in ovarian cancer is likely driven by a cassette of genes rather than by a single oncogene. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. (C) 2008 Wiley-Liss, Inc.
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收藏
页码:481 / 489
页数:9
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