Abnormalities in the p34(cdc2)-related PITSLRE protein kinase gene complex(CDC2L) on chromosome band 1p36 in melanoma

The two genes encoding the PITSLRE protein kinase isoforms, CDC2L1 and CDC2 L2, are localized to human chromosome band 1p36. The PITSLRE protein kinase s are a part of the p34(cdc2) supergene family. Several protein products of the CDC2L locus may be effector(s) in apoptotic signaling. The larger PITS LRE p110 isoforms appear to regulate some aspect of RNA splicing/transcript ion during the cell cycle. One or more of these genes may function as tumor suppressor genes in melanoma. Using fluorescence in situ hybridization, on e allele of the CDC2L gene complex on chromosome 2 was either deleted or tr anslocated in 8 of 14 different melanoma cell lines. We also observed mutat ions in the 5' promoter region of the CDC2L1 gene in four different cell li nes relative to normal melanocytes using PCR-SSCP analysis and direct DNA s equencing. Western blot analysis revealed decreased level of PITSLRE protei n expression in several cell lines, as well as in four surgical malignant m elanoma specimens relative to normal melanocytes. Thus, the decreased PITSL RE protein expression appears to result from deletion of the CDC2L alleles and possibly by mutations within the 5' promoter region. We propose that ab errations in the CDC2L genes may contribute to the pathogenesis or progress ion of melanoma. (C) Elsevier Science Inc., 1998.