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 MTS1) encodes a negative regulator of the cell cycle. This gene, located in 9p21, is mutated or homozygously deleted in a high percentage of tumor 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 cell liner. No DNA abnormalities were found in primary tumors. Conversely, p16(INK4) gene structural alterations, deletions and point mutations were found in 4 thyroid cell lines. The expression of the 2 different p16(INK4) mRNAs, the p16 alpha and p16 beta transcripts, was determined by RNA-PCR experiments. All the primary thyroid tumors expressed the beta transcript, while the p16 alpha was barely detectable. The thyroid 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 that loss of p16(INK4) function is not directly involved in the process of thyroid-tumor development, but it probably gives cells in tissue culture a selective growth advantage. (C) 1996 Wiley-Liss, Inc.