Forgacs E, Wren J D, Kamibayashi C, Kondo M, Xu X L, Markowitz S, Tomlinson G E, Muller C Y, Gazdar A F, Garner H R, Minna J D
The Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, TX 75390-8593, USA.
Oncogene. 2001 Feb 22;20(8):1005-9. doi: 10.1038/sj.onc.1204211.
RepX represents a new informatics approach to probe the UniGene database for potentially polymorphic repeat sequences in the open reading frame (ORF) of genes, 56% of which were found to be actually polymorphic. We now have performed mutational analysis of 17 such sites in genes not found to be polymorphic (<0.03 frequency) in a large panel of human cancer genomic DNAs derived from 31 lung, 21 breast, seven ovarian, 21 (13 microsatellite instability (MSI)+ and eight MSI-) colorectal cancer cell lines. In the lung, breast and ovarian tumor DNAs we found no mutations (<0.03-0.04 rate of tumor associated open reading frame mutations) in these sequences. By contrast, 18 MSI+ colorectal cancers (13 cancer cell lines and five primary tumors) with mismatch repair defects exhibited six mutations in three of the 17 genes (SREBP-2, TAN-1, GR6) (P<0.000003 compared to all other cancers tested). We conclude that coding region microsatellite alterations are rare in lung, breast, ovarian carcinomas and MSI (-) colorectal cancers, but are relatively frequent in MSI (+) colorectal cancers with mismatch repair deficits.
RepX代表了一种新的信息学方法，用于在基因的开放阅读框（ORF）中探测UniGene数据库中潜在的多态性重复序列，其中56%被发现实际上是多态的。我们现在对来自31个肺癌、21个乳腺癌、7个卵巢癌、21个（13个微卫星不稳定（MSI）+和8个MSI-）结肠癌细胞系的大量人类癌症基因组DNA中未发现多态性（频率<0.03）的基因中的17个此类位点进行了突变分析。在肺癌、乳腺癌和卵巢癌肿瘤DNA中，我们在这些序列中未发现突变（肿瘤相关开放阅读框突变率<0.03-0.04）。相比之下，18个具有错配修复缺陷的MSI+结肠直肠癌（13个癌细胞系和5个原发性肿瘤）在17个基因中的3个（SREBP-2、TAN-1、GR6）中出现了6个突变（与所有其他测试癌症相比，P<0.000003）。我们得出结论，编码区微卫星改变在肺癌、乳腺癌、卵巢癌和MSI（-）结肠直肠癌中很少见，但在具有错配修复缺陷的MSI（+）结肠直肠癌中相对常见。
