Expression Profiles in Stage II Colon Cancer According to APC Gene Status

Abstract

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.

Figure 1

Hierarchical clustering of 86 stage II colon adenocarcinomas of MSS type. Unsupervised analysis was done on the 86 RNA selected according to the inclusion criteria (stage II, colon, MSS type) within tumor samples of the COL2 project (Table W2). Tumors from different origins were equally distributed within the different branches (top of the clustering): 32 from Bordeaux (BER, black), 28 from Nice (CAL, orange), 19 from Marseille (IPC, cyan), 6 from Paris AP-HP (3 from Lariboisière hospital [LAR, green] and 3 from Saint-Antoine hospital [STA, brown]), and 1 from Nantes (NAN, yellow). The occurrence (black) or not (white) of distant metastases is given at the bottom followed by the APC status. Mutations are presented in pink or light brown if occurring before or after codon 1265, respectively; dark pink shows mutations leading before the β-catenin-binding domain starting at codon 1020.