IDENTIFICATION OF A NOVEL PHOSPHOLIPASE-C FAMILY GENE AT CHROMOSOME 2Q33 THAT IS HOMOZYGOUSLY DELETED IN HUMAN SMALL-CELL LUNG-CARCINOMA

Since a considerably high incidence of allelic loss on chromosome 2q was detected in lung carcinoma and a homozygous deletion at chromosome 2q33 was detected in a small cell lung carcinoma cell line, NCI-HSP, a novel tumor suppressor gene has been suggested to be present in this chromosomal region, In the present study, we constructed a cosmid contig map covering the homozygous deleted region, which was estimated as being 220 kbp in size, and identified a gene from the deleted region, All of the coding exons of this gene were homozygously deleted in this cell line, while a 5'-non-coding exons was retained. Since the gene encodes a protein with striking similarity to several members of a family of phospholipase C, we designated this gene as PLC-L (phospholipase C-deleted in lung carcinoma). The PLC-L gene was expressed in a variety of fetal and adult organs including the lung, However, its expression was greatly reduced in seven of 13 (53.8%) of small cell lung carcinoma and 13 of 15 (86.7%) of non-small cell lung carcinoma cell lines, Since its homology to phospholipase C genes suggests the involvement of the PLC-L gene in inositol phospholipid-based intracellular signaling cascade, it is possible that aberrant expression of the PLC-L gene contributes to the genesis or progression of human lung carcinoma.