Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours.
The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg----His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines.
Wright
P A
PA
CRC Thyroid Tumour Biology Research Group, Department of Pathology, University of Wales College of Medicine, Cardiff, UK.
Lemoine
N R
NR
Goretzki
P E
PE
Wyllie
F S
FS
Bond
J
J
Hughes
C
C
Röher
H D
HD
Williams
E D
ED
Wynford-Thomas
D
D
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53