Gene rearrangements in radiation-induced thyroid carcinogenesis

Medical and Pediatric Oncology
H M Rabes

Abstract

Radiation is an accepted risk factor for thyroid carcinogenesis in children. Recent observations in large cohorts of children and young adults who developed papillary thyroid carcinomas (PTC) related to accidental radiation exposure after the Chernobyl reactor accident revealed typical genetic aberrations shedding light on genetic determinants and mechanisms of radiation-induced carcinogenesis. A molecular genetic analysis was performed on 191 post-Chernobyl PTC by RT-PCR, multiplex PCR, DNA sequencing, and in some cases 5'RACE. Determination of point mutations was by means of PCR and either allele-specific oligonucleotide hybridization or SSCP and DNA sequencing. In various sporadic thyroid tumor types of adults structural genetic aberrations have been found involving mutations of RAS (codon 12, 13, 61), p53 (exons 5 to 8), Gsalpha (codon 201 and 227), and, at a low prevalence, the receptor tyrosine kinases RET or NTRK1. In contrast, in radiation-induced PTC of children RET rearrangements are by far the most prevalent genetic aberrations. In these RET rearrangements, the transmembrane and extracellular domains of RET are lost, and are replaced by parts of other genes at the 5' end. These genes always contain coiled-coil domain...Continue Reading

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