Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Japan.
Arch Dermatol Res. 1998 Apr;290(4):175-80. doi: 10.1007/s004030050286.
Mutations of p16 and p15 suppressor oncogenes and the replication errors in six microsatellite loci in sporadic malignant melanomas were analyzed. Four (9.1%) homozygous deletions of both p16 and p15 genes and one point mutation (2.3%) in the p15 gene were detected among 44 primary melanoma samples. One mutation in each of the p16 and p15 genes was observed in ten metastatic lesions. Eight (18.2%) replication errors were detected in three microsatellite loci in the primary melanoma samples, but no replication error was detected in the metastatic samples. None of the samples showed the alteration of p16/p15 genes and the replication errors concomitantly. These results suggest that (1) the homozygous deletions of p16/p15 genes and the replication errors may occur in rather early stages of melanoma tumorigenesis, while the p16/p15 gene mutation may occur in later stages, and (2) the p16 and p15 gene mutations in sporadic malignant melanomas might not be induced by the defect in mismatch repair, implying that p16 as well as p15 gene alterations may play an important role in the pathogenesis of sporadic malignant melanomas.
分析了散发性恶性黑色素瘤中p16和p15抑癌基因的突变以及六个微卫星位点的复制错误。在44个原发性黑色素瘤样本中，检测到4例（9.1%）p16和p15基因均为纯合缺失，1例（2.3%）p15基因存在点突变。在10个转移病灶中，分别观察到p16和p15基因各有1例突变。在原发性黑色素瘤样本的三个微卫星位点中检测到8例（18.2%）复制错误，但在转移样本中未检测到复制错误。没有样本同时显示p16/p15基因改变和复制错误。这些结果表明：（1）p16/p15基因的纯合缺失和复制错误可能发生在黑色素瘤肿瘤发生的相当早期阶段，而p16/p15基因突变可能发生在后期阶段；（2）散发性恶性黑色素瘤中的p16和p15基因突变可能不是由错配修复缺陷诱导的，这意味着p16以及p15基因改变可能在散发性恶性黑色素瘤的发病机制中起重要作用。
