Association of RET codon 691 polymorphism in radiation-induced human thyroid tumours with C-cell hyperplasia in peritumoural tissue.
The RET proto-oncogene encodes a protein structurally related to transmembrane receptors with an intracellular tyrosine kinase domain. In human thyroid gland, the RET proto-oncogene is normally expressed in parafollicular C-cells. Thyroid C-cell hyperplasia is associated with inherited medullary thyroid carcinomas and is considered as a pre-neoplastic stage of C-cells disease. It has also been observed in thyroid tissues adjacent to follicular and papillary carcinomas. In order to study the relationship between a misfunctioning of the RET proto-oncogene and the presence of C-cell hyperplasia, we compared a series of thyroid glands presenting sporadic or radiation-associated tumours, as well as samples of unrelated normal thyroid tissues, for alteration in exons 10 and 11 of the gene and for the presence or absence of C-cell hyperplasia. Here we report a significantly higher frequency of C-cell hyperplasia present in peritumoural thyroid tissues of radiation-induced epithelial thyroid tumours, than in peritumoural of sporadic thyroid tumours or in control normal thyroid tissues (P=0.001). A G691S RET polymorphism was present with a higher frequency in radiation-induced epithelial thyroid tumours (55%) than in sporadic tumours (20%) and in control normal thyroid tissues (15%). Interestingly, this polymorphism was associated in the majority (88%) of radiation-induced tumours with a C-cell hyperplasia in the peritumoural tissues. Several explanations for this association are discussed.
Bounacer
A
A
Laboratoire d'Instabilité Génétique et Cancer (UPR 2169), Institut de Recherches sur le Cancer, C.N.R.S.-IFR 89, B.P. no 8, 94801 Villejuif Cedex, France. BounacerA@cf.ac.uk
Du Villard
J A
JA
Wicker
R
R
Caillou
B
B
Schlumberger
M
M
Sarasin
A
A
Suárez
H G
HG
D000236:Adenoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004307:Dose-Response Relationship, Radiation; D029721:Drosophila Proteins; D004847:Epithelial Cells / Q000473:pathology / Q000528:radiation effects; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology
D003062:Codon; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila