Physical and transcriptional map of a 311-kb segment of chromosome 18q21, a candidate lung tumor suppressor locus.
Here, we report the complete genomic sequence and the characterization of the 311-kb region of 18q21, a candidate tumor suppressor locus containing a region of homozygous deletion in a lung cancer cell line, Ma29. This region contained two known genes, SMAD4 and ME2 (mitochondrial malate oxydoreductase), and two novel genes, D29 (deleted in Ma29 HGMW-approved symbol ELAC1), encoding an evolutionarily conserved protein, and B29 (beside the Ma29 deletion HGMW-approved symbol C18orf3), with no significant homology to any known genes. The deleted DNA segment in Ma29, which was estimated to be 195 kb in size, included all the coding exons of ME2 and D29, but not the coding exons of SMAD4 and B29. The deleted region also included exon 0, a 5'-noncoding exon, of SMAD4, and the expression of SMAD4 was greatly reduced in Ma29 cells. Mutations of SMAD4 and D29 were detected in 1 of 45 lung cancer cell lines examined, while those of ME2 and B29 were not detected, indicating that these four genes are not major targets for 18q21 deletions. The physical and transcriptional map constructed in this study will provide basic information for the identification of a tumor suppressor gene(s) at 18q21 involved in lung carcinogenesis.
Yanaihara
N
N
Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan.
Kohno
T
T
Takakura
S
S
Takei
K
K
Otsuka
A
A
Sunaga
N
N
Takahashi
M
M
Yamazaki
M
M
Tashiro
H
H
Fukuzumi
Y
Y
Fujimori
Y
Y
Hagiwara
K
K
Tanaka
T
T
Yokota
J
J
D015703:Antigens, CD / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051925:CD79 Antigens; D002887:Chromosomes, Human, Pair 18; D020451:Contig Mapping; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D051901:Smad4 Protein; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015703:Antigens, CD; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051925:CD79 Antigens; C497883:CD79B protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C430097:ELAC1 protein, human; C430098:MRO protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; D015534:Trans-Activators; D000073940:Transcription Factor 4; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins