ABNORMALITIES IN THE CDKN2 (P16(INK4) MTS-1) GENE IN HUMAN-MELANOMA CELLS - RELEVANCE TO TUMOR-GROWTH AND METASTASIS/

The inhibitor of cyclin-dependent kinase 4, CDKN2 (also known as p16(I NK4) Or MTS-1, multiple tumor suppressor gene 1), has been mapped to 9 p21, The gene has been shown to be deleted or mutated in high frequenc y in human melanoma cell lines and familial melanoma patients, suggest ing that it could be a melanoma suppressor gene. How these observation s are related to tumorigenicity and metastasis of human melanoma is no t clear however, To test the role of CDW2 in human melanoma metastasis , 14 human melanoma cell lines with different metastatic abilities in nude mice were analysed for possible abnormalities in the CDKN2 gene, Homozygous deletions that resulted in a lack of gene expression were f ound in six of 14 cell lines tested. SSCP-direct sequencing revealed p oint mutations in three other cell lines, One cell line displayed CC t o TT transitions which constitute a hallmark of ultraviolet-induced DN A damage, Overall, abnormalities in the CDKN2 gene were found in nine of 14 (64%) cell lines tested, Homozygous deletion and lack of gene ex pression were found in several low tumorigenic and nonmetastatic melan oma lines, whereas other metastatic cells did not exhibit abnormalitie s in the CDKN2 gene, These data suggest that the absence of normal CDK N2 does not confer growth advantage to melanoma cells in vivo and that the production of metastasis by human melanoma cells can occur in the absence of CDKN2 gene abnormalities.