Mutation analyses of 268 candidate genes in human tumor cell lines

We have performed a homozygous deletion screen on 268 candidate genes in 90 human tumor cell lines derived from multiple types of cancers. Most of the candidate genes investigated have been proposed to be involved in cellular processes that are germane to cancer progression, such as cell cycle contr ol, genome maintenance, chromatin remodeling, cell adhesion, and apoptosis. We have detected novel homozygous deletions affecting four independent loc i: Brahma-related gene (SMARCA4) on chromosome 19p in the TSU-Prl prostate and A427 lung carcinoma lines, Map Kinase Kinase 3 (MAP2K3) on 17q in the N CI-H774 lung tumor cell line, TMPRSS2 on 21q in the Ex PC-3 pancreatic carc inoma line, and Cadherin 6 (CDH6) on 5p in the SK-LU-1 lung carcinoma line. Subsequent analyses of the coding sequences of these four genes using cDNA s from a panel of tumor cell lines revealed multiple sequence variants. The results of this mutation study serve to demonstrate the feasibility of per forming high-throughput screens of candidate genes in tumor cell lines to i dentify genes that may be targeted for mutation during the development of c ancer. (C) 2001 Academic Press.