Identification of tumor suppressor candidate genes by physical and sequence mapping of the TSLC1 region of human chromosome 11q23

Loss of heterozygosity for a locus on human chromosome 11q22-23 is observed at high frequency in non-small cell lung carcinoma (NSCLC). Introduction o f a 1.1 Mb fragmented yeast artificial chromosome (YAC) mapping to this reg ion completely suppresses the tumorigenic properties of a human NSCLC cell line, A549. Smaller fragmented YACs give partial but not complete suppressi on. To further localize the gene(s) responsible for this partial suppressio n, a bacterial artificial chromosome (BAC) and Pl-based artificial chromoso me (PAC) contig was constructed, completely spanning the candidate region. End sequence generated in the construction of the BAC/PAC contig identified a previously unmapped EST and served to order genomic sequence contigs fro m the publicly available Celera Genomics (CG) and Human Genome Project (HGP ) efforts. Comparison showed that CG provided larger contigs, while HGP pro vided more coverage. Neither CG nor HGP provided complete sequence coverage , alone or in combination. The sequence was used to map 110 ESTs and to pre dict new genes, including two GenScan gene predictions that overlapped ESTs and were shown to be differentially expressed in tumorigenic and suppresse d A549 cell lines. (C) 2001 Elsevier Science B.V. All rights reserved.