Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region.
Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region.
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通过代表性差异分析鉴定胰腺癌中位于 BRCA2 区域内的纯合缺失。
DOI：
10.1073/pnas.92.13.5950
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发表时间：
1995
影响因子：
11.1
通讯作者：
Trent,JM
中科院分区：
文献类型：
--
作者：
Schutte,M;daCosta,LT;Hahn,SA;Moskaluk,C;Hoque,AT;Rozenblum,E;Weinstein,CL;Bittner,M;Meltzer,PS;Trent,JM
纯合缺失是发现几个肿瘤抑制基因的核心，但它们的发现往往是偶然的或直接搜索的结果。最近描述的技术[Lisitsyn，N.，Lisitsyn，N. & Wigler，M.（1993）Science 259，946-951]提供了以无偏见的方式有效地发现此类事件的潜力。本文介绍了代表性差异分析（RDA）在癌症研究中的应用。我们克隆了两个DNA片段，确定了一个纯合性缺失的人胰腺癌，映射到一个1厘摩的区域在染色体13q12.3两侧的标记D13 S171和D13 S260。有趣的是，这位于最近被确定为遗传性乳腺癌易感性BRCA 2基因座的6厘摩区域内。这表明同一基因可能参与多种肿瘤类型，其功能是肿瘤抑制基因而不是显性癌基因。
Homozygous deletions have been central to the discovery of several tumor-suppressor genes, but their finding has often been either serendipitous or the result of a directed search. A recently described technique [Lisitsyn, N., Lisitsyn, N. & Wigler, M. (1993) Science 259, 946-951] held out the potential to efficiently discover such events in an unbiased manner. Here we present the application of the representational difference analysis (RDA) to the study of cancer. We cloned two DNA fragments that identified a homozygous deletion in a human pancreatic adenocarcinoma, mapping to a 1-centimorgan region at chromosome 13q12.3 flanked by the markers D13S171 and D13S260. Interestingly, this lies within the 6-centimorgan region recently identified as the BRCA2 locus of heritable breast cancer susceptibility. This suggests that the same gene may be involved in multiple tumor types and that its function is that of a tumor suppressor rather than that of a dominant oncogene.