Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus

Abstract

Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT-PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of 69% for the Belarussian cases, but of only 19% in the German patients. In contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1) similar to that in earlier investigations (diagnosed 1991-94) was obtained for cases included in our study that were diagnosed in 1993/94. The present data suggest that ret/PTC3 may be typical for radiation-associated childhood PTC with a short latency period, whereas ret/PTC1 may be a marker for later-occurring PTC of radiation-exposed adults and children. Int.

ret/PTC Activation Is Not Associated with Individual Radiation Dose Estimates in a Pilot Study of Neoplastic Thyroid Nodules Arising in Russian Children and Adults Exposed to Chernobyl Fallout

“…The rate of ret=PTC activation in the children in this study is clearly lower than the 84-87% activation rates detected in PTC cases arising following external beam irradiation (15,24,25), and may be lower than the 30-86% activation rates detected in PTCs developing after exposure to Chernobyl fallout during childhood that have been reported to date (3)(4)(5)(6)(7)(8)(9)(10)(11). However,…”

“…Analyses of radiation-associated PTC specimens usually find a higher rate of ret=PTC activation ranging from 30% to 86% (2). Even though ionizing radiation has been shown to induce ret=PTC rearrangements in thyroid cancer cell culture models, other variables such as ethnic background, age at diagnosis, and latency period between radiation exposure and development of clinically evident PTC may also have a significant impact on the prevalence rate of ret=PTC activation reported in clinical samples (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC

“…At least 16 chimeric mRNAs involving 11 different genes have been reported (reviewed in Santoro et al, 2004) of which RET/PTC1 (RET rearrangement with H4) and RET/PTC3 (RET rearrangement with RFG/ ELE1) are by far the most common . The incidence of RET/PTC in radiation-induced childhood PTCs is in the range of 50-70% (Klugbauer et al, 1995;Smida et al, 1999;Thomas et al, 1999;Rabes et al, 2000), whereas in sporadic papillary carcinomas in adults the incidence is somewhat lower (5-30%) (Jhiang and Mazzaferri, 1994). However, the identification of RET/PTC in other common thyroid tumour histotypes such as oncocytic adenomas and carcinomas (Cheung et al, 2000), and even in hyperplastic thyroid nodules (Ishizaka et al, 1991;Elisei et al, 2001) and Hashimoto's thyroiditis (Rhoden et al, 2006), seems to challenge the validity of RET/PTC as a tumour marker and its specificity for PTC.…”

Thyroid Cancer: Molecular Characteristics of Radiation-Associated Papillary Thyroid Cancer, with a Special Reference to of Atomic Radiation Exposure

“…To date, at least 15 different types of RET/PTC rearrangements resulting from RET fusion to 12 various partner genes have been isolated, of which RET/PTC1 and RET/PTC3 are by far the most common [14,50]. RET/PTC rearrangements have frequently been found in childhood PTC with and without a radiation exposure history [11,14,18,[19][20][21][22][51][52][53]. In post-Chernobyl children with PTC, RET/PTC3 rearrangement seemed to be strongly associated with solidvariant PTC and/or with a short latent period after exposure, while RET/PTC1 rearrangement was mainly found in conventional PTC with a long latent period after exposure [11,18,19,53].…”