Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma.
The two genes encoding the PITSLRE protein kinase isoforms, CDC2L1 and CDC2L2, are localized to human chromosome band 1p36. The PITSLRE protein kinases are a part of the p34cdc2 supergene family. Several protein products of the CDC2L locus may be effector(s) in apoptotic signaling. The larger PITSLRE p110 isoforms appear to regulate some aspect of RNA splicing/transcription during the cell cycle. One or more of these genes may function as tumor suppressor genes in melanoma. Using fluorescence in situ hybridization, one allele of the CDC2L gene complex on chromosome 1 was either deleted or translocated in 8 of 14 different melanoma cell lines. We also observed mutations in the 5' promoter region of the CDC2L1 gene in four different cell lines relative to normal melanocytes using PCR-SSCP analysis and direct DNA sequencing. Western blot analysis revealed decreased level of PITSLRE protein expression in several cell lines, as well as in four surgical malignant melanoma specimens relative to normal melanocytes. Thus, the decreased PITSLRE protein expression appears to result from deletion of the CDC2L alleles and possibly by mutations within the 5' promoter region. We propose that aberrations in the CDC2L genes may contribute to the pathogenesis or progression of melanoma.
Nelson
M A
MA
Arizona Cancer Center, Tucson 85724, USA.
Ariza
M E
ME
Yang
J M
JM
Thompson
F H
FH
Taetle
R
R
Trent
J M
JM
Wymer
J
J
Massey-Brown
K
K
Broome-Powell
M
M
Easton
J
J
Lahti
J M
JM
Kidd
V J
VJ
D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D018844:Cyclin-Dependent Kinases; D004273:DNA, Neoplasm; D006801:Humans; D017403:In Situ Hybridization; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D014407:Tumor Cells, Cultured