Gene rearrangement and Chernobyl related thyroid cancers

Abstract

The increase in thyroid carcinoma post-Chernobyl has been largely confined to a specific subtype of papillary carcinoma (solid/follicular). This subtype is observed predominantly in children under 10 in unirradiated populations, but maintains a high frequency in those aged 10–15 from those areas exposed to fallout from the Chernobyl accident. The aim of this study was to link morphology with molecular biology. We examined 106 papillary carcinomas from children under the age of 15 at operation. All were examined for rearrangements of the RET oncogene by reverse transcription polymerase chain reaction (RT-PCR); a subset of these cases were also examined for mutations of the three ras oncogenes, exon 10 of the thyroid stimulating hormone receptor, associated more usually with a follicular rather than papillary morphology, and exons 5, 6, 7 and 8 of the p53 gene, commonly involved in undifferentiated thyroid carcinoma. Rearrangements of the RET oncogene were found in 44% of papillary carcinomas in which we studied fresh material; none of the tumours examined showed mutation in any of the other genes. The two rearrangements resulting from inversion of part of chromosome 10 (PTC1 and PTC3) accounted for the majority of RET rearrangements identified, with PTC1 being associated with papillary carcinomas of the classic and diffuse sclerosing variants and PTC3 with the solid/follicular variant. © 2000 Cancer Research Campaign

Diffuse sclerosing variant of papillary thyroid carcinoma: lack of BRAF mutation but occurrence of RET/PTC rearrangements

“…In order to confirm our negative BRAF results in all cases, we performed the RET/PTC rearrangement screening method originally described by Nikiforov et al, 16 which has been subsequently used by other investigators for the general demonstration of RET/ PTC rearrangements. 41,42 Using this method, we found a consistent and reproducible lack of the EC domain in all seven cases investigated, whereas the TK domain of RET could be equally consistent and reproducible demonstrated in all cases. Subsequently, RET/PTC types 1 and 3 rearrangements were found in three cases, suggesting that the remaining four cases may harbour one of the rare types of RET/PTC rearrangement.…”

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

“…Primers used to amplify ret/papillary thyroid carcinoma (PTC)1, ret/PTC3 (Santoro et al 2000), exon 15 of Braf (Nikiforova et al 2004), exons 1 and 2 of pax8/ppar 1 (Nikiforova et al 2002) and Nras (Vasko et al 2003) have been described previously. Reactions were performed in 25 ml of a PCR solution containing 4 ml cDNA, 5 mM MgCl 2 , 1 Â buffer, 4 ng/ml primer and 0.25 U Taq polymerase (Promega, Charbonnie`res, France).…”

RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase

“…Oncogenic activation of the RET kinase is a common event in papillary thyroid carcinomas (PTC) (reviewed in Vecchio and Santoro, 2000;Santoro et al, 2002), especially in patients with history of radiation exposure (Bounacer et al, 1997;Nikiforov et al, 1997;Santoro et al, 2000). Activation of the RET oncogene in PTC is the result of recombination events leading to the fusion of the RET tyrosine kinase with 5 0 -fragments of heterologous genes, the most common of which are the H4 gene, the gene encoding the RIa regulatory subunit of the cAMP-dependent protein kinase, and the RFG gene (reviewed in Puxeddu and Fagin, 2001).…”