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乳腺癌中位于8p11 - 12区域的一个1兆碱基的最小扩增子鉴定出了新的候选癌基因。

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

作者信息

Garcia Maria J, Pole Jessica C M, Chin Suet-Feung, Teschendorff Andrew, Naderi Ali, Ozdag Hilal, Vias Maria, Kranjac Tanja, Subkhankulova Tatiana, Paish Claire, Ellis Ian, Brenton James D, Edwards Paul A W, Caldas Carlos

机构信息

Department of Oncology, Hutchison/MRC Research Centre, Cancer Genomics Program, University of Cambridge, Hills Road, Cambridge CB2 2XZ, UK.

出版信息

Oncogene. 2005 Aug 4;24(33):5235-45. doi: 10.1038/sj.onc.1208741.

Abstract

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 profiling. 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 amplification. 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.

摘要

8p11 - 12区域的扩增是人类乳腺癌中一种已知的改变,但驱动癌基因尚未确定。我们开发了一种覆盖8p11 - 12的高分辨率比较基因组杂交阵列,并分析了33例原发性乳腺肿瘤、20例原发性卵巢肿瘤和27个乳腺癌细胞系。通过实时定量PCR和/或寡核苷酸微阵列分析对该区域的基因进行表达分析。总体而言,24%(8/33)的乳腺肿瘤、5%(1/20)的卵巢肿瘤和15%(4/27)的细胞系显示8p11 - 12扩增。我们鉴定出一个1 Mb的共同扩增片段,该片段排除了先前提出的候选基因。一些扩增基因未显示过表达,而对于其他基因,过表达并非特异性归因于扩增。基因FLJ14299、C8orf2、BRF2和RAB11FIP定位于8p11 - 12最小扩增子内,其中两个具有与致癌作用一致的推定功能,这四个基因在扩增和过表达之间显示出强烈的相关性,因此是8p12处最佳的候选驱动癌基因。

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