HIGH-FREQUENCY DELETION OF THE TUMOR-SUPPRESSOR GENE P16(INK4A) (MTS1) IN HUMAN THYROID-CANCER CELL-LINES

p16(INK4a) (MTS1) is an important negative regulator of mammalian cell proliferation, acting via inhibition of CDK4icyclin D-dependent phosp horylation of pRb to prevent progression through the G1 phase of the c ell cycle. Loss of p16 activity by either gene deletion, mutation or t ranscriptional inactivation has now been found in a wide range of huma n cancers of both epithelial and mesenchymal origin, at a frequency ri valling that of p53 mutation. As a first step towards investigating it s possible role as a tumour suppressor gene in thyroid tumorigenesis, we have carried out a Southern blot analysis of the p16 gene locus in a series of cell lines derived from differentiated human thyroid cance rs. Homozygous deletion of the entire p16 coding sequence was observed in two of three follicular and two of four papillary cancer cell line s; but not in normal tissue or normal cells immortalised by SV40 T ant igen. Given the co-existence of p16 abnormalities in primary tumours a nd cell lines observed in other tumour types. this high frequency of d eletion suggests that p16 is a key tumour suppressor gene in the genes is of differentiated thyroid cancer.