Centre de Recherche en Cancérologie de Marseille, INSERM, UMR891, Marseille, France.
Transl Oncol. 2012 Apr;5(2):72-6. doi: 10.1593/tlo.11325. Epub 2012 Apr 1.
Colorectal cancer is one of the most common cancers in the world. Histoclinical staging is efficient, but combination with molecular markers may improve the classification of stage II cancers. Several tumor-suppressor genes have been associated with colorectal cancer, and the most frequent allelic losses have been extensively studied for their prognosis effect, but the results remain controversial. In a previous study, we found a possible influence of the chromosome 5 status in the development of liver metastases in stage II colon cancers. We have here investigated the role of the APC gene, located in chromosome arm 5q, in a series of 183 colon adenocarcinomas through a combined analysis of gene expression, mutation, allelic loss and promoter methylation, and metastasis occurrence. Point mutations were found in 73% of cases and allelic losses were found in 39%; 59% of tumors presented with a biallelic inactivation, with a very strong interdependence of the two APC hits (P = 2.1 x 10(-9)). No association was found between expression, number and type of APC alterations, and metastatic evolution. Our results show that the determination of APC status cannot help in the prediction of metastasis and cannot be used to subclassify stage II colon cancers.
结直肠癌是世界上最常见的癌症之一。组织临床分期是有效的,但与分子标志物相结合可能会改善 II 期癌症的分类。已经有几个肿瘤抑制基因与结直肠癌相关联,并且已经对最常见的等位基因缺失进行了广泛研究,以评估其预后效果,但结果仍存在争议。在之前的一项研究中,我们发现染色体 5 状态可能会影响 II 期结肠癌肝转移的发生。我们通过联合分析基因表达、突变、等位基因缺失和启动子甲基化以及转移发生情况,研究了位于染色体 5q 臂上的 APC 基因在 183 例结肠腺癌中的作用。我们发现 73%的病例存在点突变,39%的病例存在等位基因缺失;59%的肿瘤表现为双等位基因失活,两个 APC 靶点的相互依赖性非常强(P = 2.1 x 10(-9))。APC 改变的表达、数量和类型与转移进化之间没有关联。我们的结果表明,APC 状态的确定不能帮助预测转移,也不能用于对 II 期结肠癌进行亚分类。