Multiple chromosomal aberrations and 11p allelotyping in lung cancer cell lines

Cytogenetic and molecular genetic studies have implicated many chromosomal aberrations in the pathogenesis of lung cancer. Deletions on 3p and 9p are presently the primary target for positional cloning of putative tumor suppressor genes. We have recently reported frequent loss of heterozygosity in three separate regions (HRAS, D11S12, D11S16) on 11p in freshly resected lung cancer specimens. Here we report cytogenetic and molecular genetic analyses of 26 permanently growing human lung cancer cell lines. Deletions indicating regions which may harbor potential tumor suppressor genes were found in 5/9 cell lines on 2p, 5/9 on 2q, 6/9 on 3p, 7/9 on 3q, 5/9 on 6q, 3/9 on 9p, 5/9 on 11p, and 6/9 on 13q. Reduction to hemizygosity or a statistically significant increase in the frequency of homozygosity on 11p was found for all markers investigated except for ST5 (D11S832E). Eight of twenty-six (31%) cell lines were hemizygous for D11S12 and 9/26 (35%) for D11S16. Seventeen of eighteen (94%) cell lines were homozygous for PTH (expected homozygosity, 53%), 15/15 (100%) for WT1 (expected homozygosity, 55%), and 16/18 (89%) for CAT (expected homozygosity, 50%). These results confirm the notion that 11p harbors several putative tumor suppressor genes which may become inactivated at different stages of tumor development and progression. They also provide a basis for selecting cell lines for genetic complementation specifically targeted at the regions described.