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 of a 1.1 Mb fragmented yeast artificial chromosome (YAC) mapping to this region completely suppresses the tumorigenic properties of a human NSCLC cell line, A549. Smaller fragmented YACs give partial but not complete suppression. To further localize the gene(s) responsible for this partial suppression, a bacterial artificial chromosome (BAC) and P1-based artificial chromosome (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 from the publicly available Celera Genomics (CG) and Human Genome Project (HGP) efforts. Comparison showed that CG provided larger contigs, while HGP provided more coverage. Neither CG nor HGP provided complete sequence coverage, alone or in combination. The sequence was used to map 110 ESTs and to predict new genes, including two GenScan gene predictions that overlapped ESTs and were shown to be differentially expressed in tumorigenic and suppressed A549 cell lines.
Pletcher
M T
MT
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2105, USA.
Nobukuni
T
T
Fukuhara
H
H
Kuramochi
M
M
Maruyama
T
T
Sekiya
T
T
Sussan
T
T
Isomura
M
M
Murakami
Y
Y
Reeves
R H
RH
D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D020451:Contig Mapping; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D004273:DNA, Neoplasm; D007136:Immunoglobulins; D008565:Membrane Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins