Risinger J I, Hayes A K, Berchuck A, Barrett J C
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Cancer Res. 1997 Nov 1;57(21):4736-8.
Endometrial carcinomas represent the most common gynecological cancer in the United States, yet the molecular genetic events that underlie the development of these tumors remain obscure. Chromosome 10 is implicated in the pathogenesis of endometrial carcinoma based on loss of heterozygosity (LOH), comparative genomic hybridization, and cytogenetics. Recently, a potential tumor suppressor gene, PTEN/MMAC1, with homology to dual-specificity phosphatases and to the cytoskeletal proteins tensin and auxillin was identified on chromosome 10. This gene is mutated in several types of advanced tumors that display frequent LOH on chromosome 10, most notably glioblastomas. Additionally, germ-line mutations of PTEN/MMAC1 are responsible for several familial neoplastic disorders, including Cowden disease and Bannayan-Zonana syndrome. Because this locus is included in the region of LOH in many endometrial carcinomas, we examined 70 endometrial carcinomas for alterations in PTEN/MMAC1. Somatic mutations were detected in 24 cases (34%) including 21 cases that resulted in premature truncation of the protein, 2 tumors with missense alterations in the conserved phosphatase domain, and 1 tumor with a large insertion. These data indicate that PTEN/MMAC1 is more commonly mutated than any other known gene in endometrial cancers.
子宫内膜癌是美国最常见的妇科癌症，然而这些肿瘤发生发展背后的分子遗传学事件仍不清楚。基于杂合性缺失（LOH）、比较基因组杂交和细胞遗传学研究，10号染色体与子宫内膜癌的发病机制有关。最近，在10号染色体上发现了一个潜在的抑癌基因PTEN/MMAC1，它与双特异性磷酸酶以及细胞骨架蛋白张力蛋白和辅助蛋白有同源性。该基因在几种10号染色体上频繁发生杂合性缺失的晚期肿瘤中发生突变，最显著的是胶质母细胞瘤。此外，PTEN/MMAC1的种系突变与几种家族性肿瘤疾病有关，包括考登病和班纳扬-佐纳纳综合征。由于该基因座在许多子宫内膜癌的杂合性缺失区域内，我们检测了70例子宫内膜癌中PTEN/MMAC1的改变。在24例（34%）病例中检测到体细胞突变，其中21例导致蛋白质过早截断，2例肿瘤在保守的磷酸酶结构域有错义改变，1例肿瘤有大片段插入。这些数据表明，PTEN/MMAC1在子宫内膜癌中的突变比任何其他已知基因都更常见。
