High frequency deletion of the tumour suppressor gene P16INK4a (MTS1) in human thyroid cancer cell lines.
p16INK4a (MTS1) is an important negative regulator of mammalian cell proliferation, acting via inhibition of CDK4/cyclin D-dependent phosphorylation of pRb to prevent progression through the G1 phase of the cell cycle. Loss of p16 activity by either gene deletion, mutation or transcriptional inactivation has now been found in a wide range of human cancers of both epithelial and mesenchymal origin, at a frequency rivalling that of p53 mutation. As a first step towards investigating its 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 cancers. Homozygous deletion of the entire p16 coding sequence was observed in two of three follicular and two of four papillary cancer cell lines, but not in normal tissue or normal cells immortalised by SV40 T antigen. Given the co-existence of p16 abnormalities in primary tumours and cell lines observed in other tumour types, this high frequency of deletion suggests that p16 is a key tumour suppressor gene in the genesis of differentiated thyroid cancer.
Jones
C J
CJ
Department of Pathology, University of Wales College of Medicine, Cardiff, UK.
Shaw
J J
JJ
Wyllie
F S
FS
Gaillard
N
N
Schlumberger
M
M
Wynford-Thomas
D
D
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D011518:Proto-Oncogene Proteins; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015342:DNA Probes; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases