Peinado M, Fernandezrenart M, Capella G, Wilson L, Perucho M
CALIF INST BIOL RES,11099 N TORREY PINES RD,LA JOLLA,CA 92037.
Int J Oncol. 1993 Feb;2(2):123-34.
Mutations in the p53 tumor suppressor gene have been analyzed in 196 colorectal tumors previously analyzed for mutations at codons 12 and 13 of the c-K-ras and N-ras oncogenes by a combination of Single Strand Conformation Polymorphism (SSCP) and Cycle Sequencing (CS) using total cellular RNA. Mutations were detected in 3 of 21 adenomas, 84 of 149 primary carcinomas, and 11 of 18 hepatic metastases. Over half of the tumors were homozygous for the mutant p53 allele at the mRNA level. Although deletions were detected in 5 tumors, missense mutations were the most frequent. The spectrum of 63 point mutations was heterogeneous, with all possible nucleotide substitutions ocurring at least once. No correlation was found between the spectrum of p53 gene mutations and the age, sex, race of the cancer patients or the anatomical localization of the tumors, although mutations were significantly more frequent in tumors of the distal colon. Mutations in the p53 gene did not correlate with mutations in the c-K-ras gene, indicating that colorectal cancer can develop through pathways independent not only of the presence of mutations in any of these genes but also of their cooperation.
利用总细胞RNA，通过单链构象多态性（SSCP）和循环测序（CS）相结合的方法，对196例结肠直肠癌肿瘤进行了分析，这些肿瘤之前已针对c-K-ras和N-ras癌基因的第12和13密码子的突变进行过分析。在21例腺瘤中有3例、149例原发性癌中有84例以及18例肝转移瘤中有11例检测到了突变。超过半数的肿瘤在mRNA水平上p53突变等位基因为纯合子。虽然在5例肿瘤中检测到了缺失，但错义突变最为常见。63个点突变的谱是异质的，所有可能的核苷酸替换至少出现一次。尽管在远端结肠癌肿瘤中突变明显更为频繁，但未发现p53基因突变谱与癌症患者的年龄、性别、种族或肿瘤的解剖定位之间存在相关性。p53基因的突变与c-K-ras基因的突变不相关，这表明结直肠癌可以通过不仅独立于这些基因中任何一个基因的突变存在而且独立于它们之间协同作用的途径发生发展。
