p53 mutations in childhood thyroid tumours from Belarus and in thyroid tumours without radiation history.
Mutations in the p53 tumour-suppressor gene (exons 5-8) were investigated in 31 Belarussian childhood thyroid tumours (24 cases of papillary thyroid carcinoma, 3 benign tumours and 2 cases each of thyroiditis and goiter); 33 thyroid tumours from juveniles and adults without radiation exposures (25 carcinomas of various histological types, including 11 papillary carcinomas and 8 adenomas) and 6 tumours from adults (4 papillary carcinomas, 1 adenoma, 1 goiter) served as controls. The mutational spectrum of p53 differed greatly between the childhood thyroid carcinomas from Belarus and the control groups. In the control groups of 29 malignant thyroid tumours, 7 different mutations were detected on exons 5-8, none of which occurred among the 15 papillary carcinomas in this group. Five mutations were found in tissue samples of the 24 childhood papillary carcinomas, and they were all the same p53 point mutation (CGA --> CGG) on codon 213 of exon 6. To determine whether this mutation is simply a polymorphism or whether it is specific to the tumour cells, laser-assisted microdissection was applied to collect various areas of tumorous and non-tumorous cells (10-20 cells per sample) from each paraffin-embedded tissue section of 8 of the papillary thyroid carcinomas. Using PCR-SSCP and sequence analysis on these cells, the very same p53 mutation on codon 213 was detected in various microdissected tumour samples of 2 cases, but it was not found in any microdissected non-tumorous sample. The exclusive occurrence of this p53 mutation in selective microdissected samples of tumour cells, even as homozygous mutation in 1 case, reflects a distinct tumour heterogeneity within papillary childhood thyroid carcinomas.
Smida
J
J
Institute of Radiation Biology, Ludwig-Maximilians-University, Munich, Germany.
Zitzelsberger
H
H
Kellerer
A M
AM
Lehmann
L
L
Minkus
G
G
Negele
T
T
Spelsberg
F
F
Hieber
L
L
Demidchik
E P
EP
Lengfelder
E
E
Bauchinger
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000209:etiology / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics; D002648:Child; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D002094:Republic of Belarus; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*