Dix B R, Robbins P D, Spagnolo D V, Padovan G L, House A K, Iacopetta B J
Department of Surgery, University of Western Australia, Perth, Australia.
Diagn Mol Pathol. 1995 Dec;4(4):261-5. doi: 10.1097/00019606-199512000-00006.
Mutations to the K-ras oncogene and p53 tumor suppressor gene are two of the most common genetic lesions in human cancers. In the present study we examined the clonality of colorectal tumors with respect to each of these genetic alterations. Screening for mutations was carried out using the polymerase chain reaction-based technique of single-strand conformation polymorphism. Eleven primary colorectal adenocarcinomas and two secondary adenocarcinomas were analyzed at four different sites within the tumor. Involved pericolic lymph nodes were collected from nine of these cases, a metastatic deposit in the liver was obtained in one case, and adjacent adenomatous lesions were collected in two cases. Seven tumors contained mutations in either the K-ras or p53 genes. In all cases, DNA derived from multiple sites within an individual tumor or metastatic deposits arising from that tumor showed the same pattern of gene mutation. Immunohistochemical staining for p53 protein overexpression also showed similar patterns of reactivity within individual tumors and their metastatic deposits. These results suggest that the major clonal expansion of colorectal carcinomas occurs after the acquisition of mutations in these genes. Our results also indicate that sampling errors are unlikely to occur in molecular studies aimed at defining the role of these genes in colorectal cancer progression.
K-ras癌基因和p53肿瘤抑制基因的突变是人类癌症中最常见的两种基因损伤。在本研究中，我们针对这些基因改变中的每一种，研究了结直肠癌的克隆性。使用基于聚合酶链反应的单链构象多态性技术进行突变筛查。对11例原发性结直肠癌和2例继发性腺癌在肿瘤内的四个不同部位进行了分析。从其中9例病例中收集了受累的结肠旁淋巴结，1例获得了肝脏转移灶，2例收集了相邻的腺瘤性病变。7个肿瘤在K-ras或p53基因中存在突变。在所有病例中，来自单个肿瘤内多个部位的DNA或该肿瘤产生的转移灶显示出相同的基因突变模式。p53蛋白过表达的免疫组织化学染色在单个肿瘤及其转移灶中也显示出相似的反应模式。这些结果表明，结直肠癌的主要克隆性扩增发生在这些基因获得突变之后。我们的结果还表明，在旨在确定这些基因在结直肠癌进展中作用的分子研究中，不太可能出现取样误差。
