Departments of Ophthalmology, and.
Pathology, UC San Diego, La Jolla, California.
Retina. 2020 Nov;40(11):2216-2220. doi: 10.1097/IAE.0000000000002732.
Uveal melanomas are associated with characteristic genetic changes. Germline mutations in mismatch repair (MMR) genes and microsatellite instability have been implicated in the development of numerous malignant neoplasms such as colon and ovarian cancers. The frequency of MMR defects in uveal melanomas has yet to be determined.
Here, we analyzed the frequency of MMR gene mutations in uveal melanoma specimens from the University of California, San Diego (UCSD), The Cancer Genome Atlas (TGCA), and the Catalogue of Somatic Mutations in Cancer (COSMIC).
We identified only two mutations in a MMR gene: one premature stop codon in the PMS gene within the UCSD cohort (0.5% frequency) and one in-frame deletion in MSH3 within the COSMIC database (0.8% frequency). We report copy number variation of MLH1 in monosomy 3 and show decreased mRNA expression of MLH1 in uveal melanoma specimens with monosomy 3. Expression levels of MLH1 were not found to correlate with the observed number of total mutations.
Overall, we show that mutations in MMR genes in uveal melanoma specimens are exceedingly rare, and although one copy of MLH1 is lost in monosomy 3, it does not seem to have pathologic consequences in uveal melanoma pathogenesis.
葡萄膜黑色素瘤与特征性的遗传改变有关。错配修复（MMR）基因和微卫星不稳定性的种系突变与许多恶性肿瘤的发生有关，如结肠癌和卵巢癌。葡萄膜黑色素瘤中 MMR 缺陷的频率尚未确定。
在这里，我们分析了加利福尼亚大学圣地亚哥分校（UCSD）、癌症基因组图谱（TCGA）和癌症体细胞突变目录（COSMIC）的葡萄膜黑色素瘤标本中 MMR 基因突变的频率。
我们仅在 UCSD 队列的 PMS 基因中发现了一个 MMR 基因突变：一个提前终止密码子（频率为 0.5%），在 COSMIC 数据库中发现了 MSH3 的一个框内缺失（频率为 0.8%）。我们报告了 MLH1 单体 3 中的拷贝数变异，并显示单体 3 中的葡萄膜黑色素瘤标本中 MLH1 的 mRNA 表达降低。MLH1 的表达水平与观察到的总突变数无关。
总的来说，我们表明葡萄膜黑色素瘤标本中 MMR 基因突变非常罕见，尽管 MLH1 的一个拷贝在单体 3 中丢失，但它似乎在葡萄膜黑色素瘤发病机制中没有病理后果。
