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-H82, 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.
Kohno
T
T
National Cancer Center Research Institute, Tokyo, Japan.
Otsuka
T
T
Takano
H
H
Yamamoto
T
T
Hamaguchi
M
M
Terada
M
M
Yokota
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003360:Cosmids; D017931:DNA Primers; D018076:DNA, Complementary; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics*
D017931:DNA Primers; D018076:DNA, Complementary; D010738:Type C Phospholipases