SHORT REPORT Mutations of the PIK3CA gene in hereditary colorectal cancers

Somatic mutations of the PIK3CA gene have recently beendetected in various human cancers, including sporadic colorectalcancer. However, mutations of the PIK3CA gene in hereditary col-orectal cancers have not been clarified. To elucidate the mutationstatus in familial adenomatous polyposis (FAP) and hereditarynonpolyposis colorectal cancer (HNPCC), which are the mostcommon hereditary colorectal cancers, we investigated PIK3CAmutations in 163 colorectal tumors, including adenomas, intramu-cosal carcinomas and invasive carcinomas. For comparison, wealso analyzed mutations of the same gene in 160 sporadic colorec-tal tumors at various histopathological stages. Analysis at exons 1,7, 9 and 20 of the PIK3CA gene revealed somatic mutations in21% (8 of 39) of FAP invasive carcinomas, 21% (7 of 34) ofHNPCC invasive carcinomas, 15% (8 of 52) of sporadic invasivecarcinomas, and 14% (7 of 50) of sporadic colorectal metastasesin the liver. Mutations in FAP and HNPCC carcinomas predo-minantly occurred in the kinase domain (exon 20), while themajority of mutations in sporadic cases occurred in the helicaldomain (exon 9). Adenomas and intramucosal carcinomas fromall patients exhibited no mutations (0 of 148). Our data suggestthat PIK3CA mutations contribute to the invasion step from intra-mucosal carcinoma to invasive carcinoma in colorectal carcino-genesis in FAP and HNPCC patients at a similar extent to thatseen in sporadic patients.