Absence of p16/MTS1 gene mutations in human prostate cancer.
The tumor suppressor gene p16/MTS1, located on chromosome 9p21, is a cell cycle regulatory gene which is frequently altered in human cancers. The role of this gene in prostate cancer is unknown. To determine the frequency of deletions and point mutations of p16/MTS1 in human prostate cancer, we examined 18 cancer and matched benign and hyperplastic tissue specimens. Deletions of p16/MTS1 were detected by semi-quantitative multiplex polymerase chain reaction in which a portion of exon 2 of the p16/MTS1 gene and a control marker, the glyceraldehyde 3-phosphate dehydrogenase gene, were amplified simultaneously. 'Cold' single-stranded conformational polymorphism (SSCP) analysis was performed to examine exons 1 and 2 of the p16/MTS1 gene for point mutations. Our data indicate no evidence for intragenic homozygous deletion in the prostate tumors. One prostate tumor and matched benign tissue showed mobility shifts. Direct DNA sequencing of the SSCP positive samples showed a G --> A transition in codon 140 which would result in an amino acid change from alanine to threonine. Our results indicate that deletions and point mutations in the p16/MTS1 gene are rare and do not play a major role in human prostate carcinogenesis.