Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types

Abstract

Allelic loss is a hallmark of tumor suppressor gene (TSG) inactivation. We have allelotyped 29 paired lymphoblastoid and lung cancer cell lines derived from 11 patients with small cell (SCLC) and 18 patients with non‐small cell lung carcinomas (NSCLC). Statistical analysis indicated that a threshold of 30% separated non‐random allelic loss from the random genetic deletions of malignancy. We have identified non‐random allelic loss at 42 of 54 (78%) specific chromosomal regions examined, with 22 regions (52%) common between the two major lung cancer histologic 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 between NSCLC and SCLC at 13 regions on eight chromosome arms (3p, 5q, 6q, 9p, 10q, 11p, 13q, and 19p). Eight homozygous deletions were present in seven cell lines at four regions, 3p12, 3p14.2, 9p21, and 10q23–25. We have also identified novel sites of chromosomal deletions. In particular, there was frequent loss at 11p13 in SCLC and loss at 6p21.3 and 13q12.3 in NSCLC. In this study, we demonstrate that a) non‐random allelic losses in lung cancer involve multiple regions; b) some losses are common to both NSCLC and SCLC subtypes, whereas others are subtype specific; c) there are genetic deletions at novel chromosomal regions; and d) several homozygous deletions have been noted. Our studies demonstrate the usefulness of continuous cell lines for detailed allelotyping, for comparing genetic abnormalities between SCLC and NSCLC, and for identifying homozygous deletions. Genes Chromosomes Cancer 21:308–319, 1998. © 1998 Wiley‐Liss, Inc.

Evidence that MIG-6 is a tumor-suppressor gene

“…Linkage analyses using microsatellite markers revealed deletions of 1p36 in nearly 50% of primary human lung cancers (Nomoto et al, 2000). Similar results were also reported in human lung cancer cell lines, including both NSCLC and small cell lung cancer (Virmani et al, 1998;Girard et al, 2000;Fujii et al, 2002). The evidence indicating the presence of a tumor-suppressor gene in 1p36 also comes from studies of mouse lung cancer.…”

Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis

“…43,44 These studies found that some LOH was common in both small cell carcinoma and non-small-cell carcinoma subtypes, whereas loss was subtype-specific in others. It has been suggested that the genetic alterations undergone by small cell carcinoma and non-smallcell carcinoma are different.…”

Role of LKB1 in lung cancer development

“…A range of atypical PJS tumours was also identified, including prostate and melanoma. Surprisingly, the highest mutation rate, hovering around 25% in multiple studies, was in lung adenocarcinomas, an established but uncommon PJSassociated tumour (Virmani et al, 1998;Sanchez-Cespedes et al, 2001) (Table 1).…”