ALLELOTYPING DEMONSTRATES COMMON AND DISTINCT PATTERNS OF CHROMOSOMALLOSS IN HUMAN LUNG-CANCER TYPES

Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation , We have allelotyped 29 paired lymphoblastoid and lung cancer cell li nes derived from I [ patients with small cell (SCLC) and 18 patients w ith non-small cell lung carcinomas (NSCLC). Statistical analysis indic ated that a threshold of 30% separated non-random allelic loss from th e random genetic deletions of malignancy, We have identified non-rando m allelic loss at 42 of 54 (78%) specific chromosamal regions examined , with 22 regions (52%) common between the two major lung cancer histo logic types. There were 3 regions (7%) with allelic loss specific for SCLC and 17 regions (41%) specific for NSCLC, Furthermore, there were significant differences in loss of heterozygosity (LOH) frequencies be tween NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6 q, 9p, 10q, 11p, 13q, and 19p). Eight homozygous deletions were presen t in seven cell lines at four regions, 3p12, 3p14.2, 9p21, and 10q23-2 5. We have also identified novel sites of chromosomal deletions, In pa rticular, there was frequent loss at [1p13 in SCLC and loss at bp21.3 and 13q12.3 in NSCLC, In this study, we demonstrate that a) non-random allelic losses in lung cancer involve multiple regions; b) some losse s are common to both NSCLC and SCLC subtypes, whereas others are subty pe specific; c) there are genetic deletions at novel chromosomal regio ns; and d) several homozygous deletions have been noted. Our studies d emonstrate the usefulness of continuous cell lines for detailed allelo typing, for comparing genetic abnormalities between SCLC and NSCLC, an d for identifying homozygous deletions. (C) 1998 Wiley-Liss, Inc.