Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas
Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas
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DOI：
10.1038/sj.onc.1201232
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发表时间：
1997-08-28
期刊：
影响因子：
8
通讯作者：
Bookstein, R
中科院分区：
文献类型：
--
作者：
MacGrogan, D;Pegram, M;Bookstein, R
据报道，18q 染色体的等位基因缺失在前列腺癌和结直肠癌中很常见，这表明 18q 上的一个或多个肿瘤抑制基因参与了这些肿瘤的发生。最近在 18q21 中鉴定出的候选肿瘤抑制基因 DPC4 基因被检查以寻找前列腺癌中失活的证据，并将结果与 结直肠癌，据报道，大约 10% 的病例中有 DPC4 突变。在这项研究中，29 例有信息性的原发性前列腺癌中，只有 3 例 (10%) 显示染色体 18q21 标记物等位基因丢失，并且在 45 例原发性或转移性病例的完整组中未检测到 DPC4 点突变或缺失。相比之下，9 例原发性结直肠肿瘤中有 5 例 (56%) 显示 18q 标记的等位基因丢失，其中之一在外显子 1 中发现体细胞获得性 G-->T 错义突变。在 12 种结直肠肿瘤细胞系中，一种在外显子 8 中显示 G-->C 错义突变，两种具有可能消除基因功能的部分纯合缺失。这些数据表明，DPC4 在前列腺肿瘤发生过程中很少发生突变，而 该基因的失活可能导致一部分结直肠癌的发生。
Allelic deletions of chromosome 18q are reported to be common in prostate and colorectal cancers, suggesting that one or more tumor suppressor genes on 18q are involved in the genesis of these neoplasms, The DPC4 gene, a recently identified candidate tumor suppressor in 18q21, was examined for evidence of inactivation in prostatic carcinomas, and results compared to those of a parallel analysis of colorectal carcinomas, for which DPC4 mutation has been reported in similar to 10% of cases, In this study, only three (10%) of 29 informative primary prostate cancers showed allelic loss of chromosome 18q21 markers, and no point mutations or deletions of DPC4 were detected in the complete set of 45 primary or metastatic cases, In contrast, five (56%) of nine primary colorectal tumors displayed allelic loss of 18q markers and in one of these a somatically acquired G-->T missense mutation was found in exon 1. Of twelve colorectal tumor cell lines, one showed a G-->C missense mutation in exon 8 and two had partial homozygous deletions that would likely abrogate gene function, These data suggest that DPC4 is rarely if ever mutated during prostatic oncogenesis, whereas inactivation of this gene may contribute to the genesis of a subset of colorectal carcinomas.