ASSOCIATION OF CDKN2A (P16) CDKN2B (P15) ALTERATIONS AND HOMOZYGOUS CHROMOSOME ARM 9P DELETIONS IN HUMAN LUNG-CARCINOMA/

To elucidate the possibility of the existence of multiple tumor suppre ssor genes on chromosome arm 9p, we performed genetic and epigenetic a nalyses of the CDKN2A/P16/MTS1 and CDKN2B/p15/MTS2 genes as well as ho mozygous deletion mapping of 9p in human lung carcinoma. To avoid over looking genetic alterations due to contamination of noncancerous cells , we examined 32 non-small cell lung carcinoma (NSCLC) and 16 small ce ll lung carcinoma (SCLC) cell lines. CDKN2A was mutated or homozygousl y deleted in 20 (63%) of 32 NSCLC cell lines, and methylation of the C pG island in the CDKN2A gene was detected in six of the 12 cell lines carrying the wild-type CDKN2A gene. Although homozygous deletions of t he CDKN2B gene were also detected in NSCLC cell lines with CDKN2A dele tions, mutation and methylation in the CDKN2B gene were infrequent. Th us, it was indicated that the CDKN2A gene rather than the CDKN2B gene plays a critical role as a tumor suppressor gene in NSCLC, Homozygous deletions on 9p were detected in 14 (44%) NSCLC cell lines. It is of n ote that two common regions of homozygous deletions were mapped proxim al to the CDKN2A and CDKN2B loci, suggesting that tumor-suppressor gen es other than CDKN2A are present on 9p. In contrast to NSCLC, homozygo us deletions on 9p as well as CDKN2A and CDKN2B alterations were infre quent in SCLC. Therefore, the pathogenetic significance of 9p alterati ons is likely to differ between SCLC and NSCLC. (C) 1998 Wiley-Liss, I nc.