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

Arvind K. Virmani, Kwun M. Fong, Dulmini Kodagoda, Donald McIntire, Jaclyn Hung, Vijay Tonk, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

171 Citations (Scopus)

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, 3p 12, 3p 14.2, 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.

Original languageEnglish (US)
Pages (from-to)308-319
Number of pages12
JournalGenes Chromosomes and Cancer
Volume21
Issue number4
DOIs
StatePublished - 1998

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Loss of Heterozygosity
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Cell Line
Gene Silencing
Tumor Suppressor Genes
Chromosomes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. / Virmani, Arvind K.; Fong, Kwun M.; Kodagoda, Dulmini; McIntire, Donald; Hung, Jaclyn; Tonk, Vijay; Minna, John D.; Gazdar, Adi F.

In: Genes Chromosomes and Cancer, Vol. 21, No. 4, 1998, p. 308-319.

Research output: Contribution to journalArticle

Virmani, Arvind K. ; Fong, Kwun M. ; Kodagoda, Dulmini ; McIntire, Donald ; Hung, Jaclyn ; Tonk, Vijay ; Minna, John D. ; Gazdar, Adi F. / Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. In: Genes Chromosomes and Cancer. 1998 ; Vol. 21, No. 4. pp. 308-319.
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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, 3p 12, 3p 14.2, 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.",
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