Corradini P, Ladetto M, Voena C, Palumbo A, Inghirami G, Knowles D M, Boccadoro M, Pileri A
Department of Medicine and Experimental Oncology, University of Torino, Italy.
Blood. 1993 May 15;81(10):2708-13.
The frequency of N- and K-ras oncogene mutations was investigated in plasma cell dyscrasias. Genomic DNAs from 128 patients were selected for this study: 30 monoclonal gammopathies of undetermined significance, 8 solitary plasmacytomas, 77 multiple myelomas (MM), and 13 plasma cell leukemias (PCL). A two-step experimental approach was devised. All samples were screened for mutations by single-strand conformation polymorphism analysis. DNA fragments displaying an altered electrophoretic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations. Ras mutations are not randomly distributed because they are detectable only in MM (9%) and PCL (30.7%). N-ras codons 12, 13, and 61 and K-ras codon 12 were found to be mutated, but N-ras codon 61 mutation was the most frequent finding (63.6%). In conclusion, ras mutations were found in PCL, and in a subset of MM characterized by advanced-stage disease and adverse prognostic parameters. Furthermore, based on our findings, it is possible to speculate that ras mutations represent a late molecular lesion in the process of multistep carcinogenesis.
在浆细胞异常增生症中研究了N-和K-ras癌基因突变的频率。本研究选取了128例患者的基因组DNA：30例意义未明的单克隆丙种球蛋白病、8例孤立性浆细胞瘤、77例多发性骨髓瘤（MM）和13例浆细胞白血病（PCL）。设计了一种两步实验方法。通过单链构象多态性分析对所有样本进行突变筛查。对电泳迁移率改变的DNA片段进一步进行直接测序，以确认并鉴定突变的性质。Ras突变并非随机分布，因为仅在MM（9%）和PCL（30.7%）中可检测到。发现N-ras密码子12、13和61以及K-ras密码子12发生了突变，但N-ras密码子61突变是最常见的发现（63.6%）。总之，在PCL以及以晚期疾病和不良预后参数为特征的一部分MM中发现了ras突变。此外，基于我们的研究结果，可以推测ras突变代表多步骤致癌过程中的晚期分子病变。
