ANALYSIS OF PTEN MMAC1 ALTERATIONS IN AERODIGESTIVE TRACT TUMORS/

PTEN/MMAC1 is a candidate tumor suppressor gene recently identified at chromosomal hand 10q23. It is mutated in sporadic brain, breast, and prostate cancer and in the germ line of patients with hereditary Cowde n disease. We searched for genetic alterations of the PTEN/MMAC1 gene in 39 primary head and neck cancers (HNSCCs), 42 primary non-small cel l lung cancers (NSCLCs), 80 pancreatic cancer xenografts, and 37 cell lines and xenografts from colon, lung, and gastric cancers. Microsatel lite analysis revealed loss of heterozygosity at markers near the gene in 41% of primary HNSCCs, 50% of NSCLCs, and 39% of the pancreatic ca ncers. Three cases of HNSCCs displayed homozygous deletion involving t he gene. We sequenced the entire coding region of the PTEN/MMAC1 gene in the remaining tumors displaying loss of heterozygosity and found on e terminating mutation in a HNSCC sample. Thus, a second inactivation event was observed in 4 of 39 primary HNSCC cases. By use of a protein truncation assay, one terminating mutation was also identified in one of eight NSCLC cell lines. Our results suggest that PTEN/MMAC1 gene i nactivation plays a role in the genesis of some tumor types.