A 1Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes

被引:129
作者
Garcia, MJ
Pole, JCM
Chin, SF
Teschendorff, A
Naderi, A
Ozdag, H
Vias, M
Kranjac, T
Subkhankulova, T
Paish, C
Ellis, I
Brenton, JD
Edwards, PAW
Caldas, C
机构
[1] Univ Cambridge, Canc Gemon Program, Dept Oncol Hutchison, MRC,Res Ctr, Cambridge CB2 2XZ, England
[2] Univ Cambridge, Dept Pathol, Res Ctr, MRC, Cambridge CB2 2XZ, England
[3] City Hosp NHS Trust, Dept Histopathol, Breast Unit, Nottingham NG5 1PB, England
基金
英国生物技术与生命科学研究理事会;
关键词
8p11-12; amplicon; breast cancer; array-CGH; minimal region of amplification; candidate oncogene;
D O I
10.1038/sj.onc.1208741
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
Amplification of 8p11-12 is a well-known alteration in human breast cancers but the driving oncogene has not been identified. We have developed a high-resolution comparative genomic hybridization array covering 8p11-12 and analysed 33 primary breast tumors, 20 primary ovarian tumors and 27 breast cancer cell lines. Expression analysis of the genes in the region was carried out by using real-time quantitative PCR and/or oligo-microarray pro. ling. In all, 24% (8/33) of the breast tumors, 5% (1/20) of the ovary tumors and 15% (4/27) of the cell lines showed 8p11-12 amplification. We identified a 1 Mb segment of common amplification that excludes previously proposed candidate genes. Some of the amplified genes did not show overexpression, whereas for others, overexpression was not specifically attributable to amplication. The genes FLJ14299, C8orf2, BRF2 and RAB11FIP, map within the 8p11-12 minimal amplicon, two have a putative function consistent with an oncogenic role, these four genes showed a strong correlation between amplification and overexpression and are therefore the best candidate driver oncogenes at 8p12.
引用
收藏
页码:5235 / 5245
页数:11
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