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Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non-small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is approximately 180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer.

Amplification of chromosome arms 3q and 5p and deletion of 3p were frequently detected in nasopharyngeal carcinoma (NPC) with comparative genomic hybridization and loss of heterozygosity studies. To identify the minimal amplified or deleted regions in these arms, structural aberrations in chromosome arms 3p, 3q, and 5p in two NPC cell lines, CNE1 and SUNE1, were studied with multiplex-color FISH (M-FISH) and chromosome region-specific probes (CRP). All CRPs, which were generated from microdissected DNA, were specific and strong in intensity, and sensitive enough to detect chromosome aberrations including translocations, deletions, and amplifications of target regions. In these two NPC cell lines, minimal regions of deletion and amplification were found at 3p12 and 3q26 approximately q27, respectively. On 5p, most of the regions were amplified as intact copies. Interregion translocations of these three arms were also observed. The amplification on 3q26 approximately q27 provided useful hints for further screening the minimal amplification at RP11-115J24 (3q26.2), containing candidate oncogene eIF-5A2. M-FISH with CRPs is thus not only useful in revealing a comprehensive picture of structural aberrations in target chromosomes, but also in narrowing down the minimal region for screening cancer-related genes.