STATUS AND EXPRESSION OF THE P16(INK)4 GENE IN HUMAN THYROID-TUMORS AND THYROID-TUMOR CELL-LINES

The p16(INK4) tumor-suppressor gene (also known as CDKN2, CDK41 and MT S1) encodes a negative regulator of the cell cycle. This gene, located in 9p21, is mutated or homozygously deleted in a high percentage of t umor cell lines and specific types of primary tumors. We have examined the status of the p16(INK4) gene in 31 thyroid tumors and 7 thyroid c ell liner. No DNA abnormalities were found in primary tumors. Converse ly, p16(INK4) gene structural alterations, deletions and point mutatio ns were found in 4 thyroid cell lines. The expression of the 2 differe nt p16(INK4) mRNAs, the p16 alpha and p16 beta transcripts, was determ ined by RNA-PCR experiments. All the primary thyroid tumors expressed the beta transcript, while the p16 alpha was barely detectable. The th yroid cell lines always expressed the p16 beta transcript, while the a transcript was absent or, whenever present, coded for a mutated form of the p16(INK4) gene product. Taken together, our results suggest tha t loss of p16(INK4) function is not directly involved in the process o f thyroid-tumor development, but it probably gives cells in tissue cul ture a selective growth advantage. (C) 1996 Wiley-Liss, Inc.