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

Tuttle, R. Michael; Lukes, Yvonne; Onstad, Lynn; Lushnikov, E F; Abrosimov, Alexander; Трошин, В. П.; Цыб, А Ф; Davis, Scott; Kopecky, Kenneth J.; Francis, Gary L.

doi:10.1089/thy.2008.0072

Cited by 25 publications

(18 citation statements)

References 28 publications

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“…RET/PTC rearrangements have been strongly associated with radiation-induced PTCs [35, 44, 45]. RET/PTC rearrangements could also be detected in sporadic PTCs, but the underlying causes are unknown.…”

Section: Discussionmentioning

confidence: 99%

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review

et al. 2016

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BackgroundThe genetic alterations of papillary thyroid carcinoma (PTC) have been reported to change over the past few decades. We performed this systematic review to further examine the trends and modifications of patient demographic, clinicopathological features and molecular profiles of PTC over time.MethodsA literature search was performed within six electronic databases to identify relevant articles. The inclusion criteria were published studies investigating BRAF mutations, RET/PTC rearrangements or RAS mutations in PTCs or classical PTCs. Two teams of reviewers independently screened titles and abstracts of all articles. Full texts of potential articles were read and extracted data were listed and stratified into an excel file according to country, city, institution, and surgical time period. Student t test and Pearson Chi-square were used to analyze the trends of demographic and clinicopathological features of PTC patients and the prevalence of each genetic alteration in individual institutions.ResultsFrom 3139 articles, we included 16 articles for final analysis. Our results showed an increasing trend of BRAF and a decreasing trend of RET/PTC prevalence over time in PTCs and classical PTCs, accompanied by an older age of PTC patients, an increase in proportion of PTMC and less aggressive behaviours of tumours.ConclusionsThe demographic and clinicopathological characteristics and molecular profile of PTCs have been changing over the past few decades. These modifications suggest changes in etiologies and risk factors of thyroid cancer that influence the tumorigenesis of PTCs.

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Section: Discussionmentioning

confidence: 99%

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review

et al. 2016

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“…It was speculated that this rearrangement might be a marker for radiation-induced tumors (7). However, more recent papers have suggested that this may be related more to the young age of the patients in the study, because frequent RET/PTC rearrangements have also been observed, with similar prevalence, in sporadic papillary carcinomas from children and young adults (8,9). These findings may therefore reflect more the association between the solid morphological subtype with RET/PTC3 rearrangement and the age of the patient at diagnosis, rather than the etiology of the tumor (5, 10).…”

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confidence: 87%

Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation

Heß

Thomas

Braselmann

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The main consequence of the Chernobyl accident has been an increase in papillary thyroid carcinomas (PTCs) in those exposed to radioactive fallout as young children. Our aim was to identify genomic alterations that are associated with exposure to radiation. We used array comparative genomic hybridization to analyze a main (n = 52) and a validation cohort (n = 28) of PTC from patients aged <25 y at operation and matched for age at diagnosis and residency. Both cohorts consisted of patients exposed and not exposed to radioiodine fallout. The study showed association of a gain on chromosome 7 (7q11.22-11.23) with exposure (false discovery rate = 0.035). Thirty-nine percent of the exposed group showed the alteration; however, it was not found in a single case from the unexposed group. This was confirmed in the validation set. Because only a subgroup of cases in the exposed groups showed gain of 7q11.22-11.23, it is likely that different molecular subgroups and routes of radiation-induced carcinogenesis exist. The candidate gene CLIP2 was specifically overexpressed in the exposed cases. In addition, the expression of the genes PMS2L11, PMS2L3, and STAG3L3 correlated with gain of 7q11.22-11.23. An enrichment of Gene Ontology terms "DNA repair" (PMS2L3, PMS2L5), "response to DNA damage stimulus" (BAZ1B, PMS2L3, PMS2L5, RFC2), and "cell-cell adhesion" (CLDN3, CLDN4) was found. This study, using matched exposed and unexposed cohorts, provides insights into the radiation-related carcinogenesis of young-onset PTC and, with the exposure-specific gain of 7q11 and overexpression of the CLIP2 gene, radiation-specific molecular markers.FISH | post-Chernobyl

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“…RET/PTC chromosomal rearrangements commonly are involved in the molecular pathogenesis of radiation-associated papillary thyroid carcinomas and ionizing radiation has been reported to induce these rearrangements in many studies (68–70), but the frequency of RET/PTC activation was not related to radiation dose in one study (71). The role of RET/PTC rearrangements in relation to thyroid nodules is much less obvious.…”

Section: Thyroid Diseasesmentioning

confidence: 97%

Non-malignant Thyroid Diseases after a Wide Range of Radiation Exposures

Ron

Brenner

2010

Radiation Research

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Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases.

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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

Cited by 25 publications

References 28 publications

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review

Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation

Non-malignant Thyroid Diseases after a Wide Range of Radiation Exposures

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