Three New Regions on Chromosome 17p13.3 Distal to p53 with Possible Tumor Suppressor Gene Involvement in Lung Cancer

Department of Chest Surgery, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-0012We investigated loss of heterozygosity (LOH) at the distal portion of the p53 gene on the short armof chromosome 17 in lung cancers in order to search for new tumor suppressor genes. The roles ofthe putative genes were also studied in terms of pathological features. One hundred and forty-fiveresected non-small cell lung cancers were examined for LOH using 11 markers mapped on, anddistal to the p53 locus, and deletion maps were constructed. Four commonly deleted regions werefound: one from TP53 to ENO3, where the p53 gene resides, and three others from ENO3 toD17S1566, D17S379 to D17S1574 and distal to ABR, with LOH frequencies almost the same as, orhigher than, at the TP53 locus. Examination of the relationship between LOH of the latter threeregions and histopathological parameters of adenocarcinomas (genetically negative for p53 muta-tion) revealed allelic losses on D17S379 to be associated with advanced lesions, while D17S513 wasmore frequently deleted in poorly differentiated tumors. These results indicate that new tumorsuppressor gene(s) may reside on these three distinctly deleted regions on chromosome 17p13.3 dis-tal to the p53 gene in lung cancer, with possible roles in progression and differentiation of adeno-carcinomas.Key words: Tumor suppressor gene — 17p13.3 — Non-small cell lung cancer — LOH — Prognosis