Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer.
We analyzed the pattern of allelic loss in 33 primary human small cell lung cancers (SCLCs) using highly informative microsatellite markers on chromosomes 2p, 3p, 5q, 6, 9, 13q, and 17p. Nineteen of these tumors (58%) displayed loss of heterozygosity on chromosome 9. Fourteen SCLCs demonstrated loss of heterozygosity for all informative markers on both chromosomal arms; two tumors demonstrated partial loss on chromosome 9p. In one tumor, a multiplex polymerase chain reaction assay disclosed a homozygous deletion at 9p21-22 including the markers IFN-alpha, D9S126, and D9S171. Two SCLCs retained all informative markers on 9p but showed allelic loss of the entire 9q arm, while one case had a partial loss of proximal 9q extending into all of 9p. Analysis of other chromosomal arms showed loss of heterozygosity on 3p (93%), 5q (75%), 6p (46%), 6q (47%), 13q (75%), and 17p (93%). It was necessary to test multiple markers at several loci because of the frequent expression of microsatellite instability that confounded our mapping efforts in SCLCs with replication errors. This study demonstrates the frequent loss of a suppressor gene locus on chromosome 9p21-22 and identifies novel suppressor loci on 6p, 6q, and 9q in primary SCLC.
Merlo, A; Gabrielson, E; Mabry, M; Vollmer, R; Baylin, SB; Sidransky, D
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