Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3

The short arm of chromosome 3 is thought to contain multiple tumor suppress or genes, because one copy of this chromosomal arm frequently is missing in carcinomas that have arisen in a variety of tissues, We have isolated a no vel gene encoding a 1755-amino acid polypeptide, through large-scale sequen cing of genomic DNA at 3p21.3, Mutational analysis of this gene by reverse transcription-PCR revealed the lack of functional transcripts and an increa se of nonfunctional RNA transcripts in a significant proportion (33%) of ca ncer cell lines and primary cancers (4 of 14 esophageal cancer cell lines, 2 of 2 renal cancer cell lines, 11 of 30 primary non-small cell lung cancer s, and 3 of 10 primary squamous cell carcinomas of the esophagus), However, no alterations of the gene itself were detected in any of the cancers exam ined, Introduction of the cDNA significantly suppressed the growth of four different cancer cell lines, two of which produced no normal transcript on their own, No such effect occurred when antisense cDNA, cDNA corresponding to an aberrant transcript, or the vector DNA alone were transfected. These data suggest that aberrant transcription of this gene, designated DLC1 (del eted in lung cancer 1), may be involved in carcinogenesis of the lung, esop hagus, and kidney.