A. The p16 or multiple tumor suppressor (MTS) 1 gene is homozygously deleted in 19/78 (24%) cell lines established from patients with non-small cell lung cancer compared to 3 of 193 (3%) cell lines established from patients with small cell lung cancer (p <0.001) but not n the normal tissue from the same patients. p16 or multiple tumor suppressor 1 mRNA and protein were not detectable among cell lines which have homozygous deletions. Homozygous deletions are present in 17 of the 57 (30%) non- small cell lung cancer cell lines studied which have normal retinoblastoma protein. B. We studied patterns of TP53 gene mutations in six patients with multiple primary cancers using polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) analysis of exons 5-8 and overexpression of p53 protein by immunohistochemical analyses. Three of the 13 tumors (one patient had three primary tumors) exhibited a mobility shift on SSCP analysis and were confirmed to have missense mutations by DNA sequencing. Immunohistochemical analysis showed 7 of 13 (54%) tumors had moderate to strong straining for TP53 for 10% or more of the tumor cells. Three of these seven tumors also had TP53 mutations.