Distinctive molecular features of radiation-induced thyroid cancers.

Papillary thyroid carcinoma (PTC) incidence increased after childhood exposure to radioactive fallout from the Chornobyl accident. We investigated PTC genomic profiles to distinguish radiation-induced versus sporadic oncogenic drivers by modeling dose and molecular characteristics by driver category: ( = 132), RAS mutation ( = 31), fusions generated from two breakpoints and <20 base pairs (bp) breakpoint gain/loss (Fusion; = 63), or ≥3 breakpoints and ≥1000 bp breakpoint loss ( = 20). The frequency of Fusion-PTC increased with increasing thyroid radiation dose, whereas all others declined.

Somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma.

Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC cases with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC cases with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm.

Prevalence of Thyroid Nodules in Residents of Ukraine Exposed as Children or Adolescents to Iodine-131 from the Chornobyl Accident.

Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). This is a cross-sectional study of radiation dose (mean = 0.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey.

Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair.

Comparative Histopathologic Analysis of "Radiogenic" and "Sporadic" Papillary Thyroid Carcinoma: Patients Born Before and After the Chernobyl Accident.

Background: The issue of whether radiation-induced thyroid cancer is pathologically different from sporadic remains not fully answered. This study compared structural characteristics and invasive features of papillary thyroid carcinoma (PTC) in two age-matched groups: patients who were children (≤4 years old) at the time of the Chernobyl accident and who lived in three regions of Ukraine most contaminated by radioactive iodine I ("radiogenic" cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to I ("sporadic" cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual I thyroid dose.

Investigation of the Relationship Between Radiation Dose and Gene Mutations and Fusions in Post-Chernobyl Thyroid Cancer.

Background: Exposure to ionizing radiation during childhood is a well-established risk factor for thyroid cancer. However, the genetic mechanisms of radiation-associated carcinogenesis remain not fully understood.

Methods: In this study, we used targeted next-generation sequencing and RNA-Seq to study 65 papillary thyroid cancers (PTCs) from patients in the Ukrainian-American cohort with measurement-based iodine-131 (I-131) thyroid doses received as a result of the Chernobyl accident.

Comparative histopathological analysis of sporadic pediatric papillary thyroid carcinoma from Japan and Ukraine.

This study set out to compare structural and invasive characteristics of sporadic papillary thyroid carcinoma (PTC) in age-matched groups of children and adolescents of Japan and Ukraine to provide detailed histopathological analysis of tumors from different geographical areas with different iodine intake. A total of 348 (160 Japanese and 188 Ukrainian) PTCs from patients without radiation history were analyzed initially as a combined pediatric group and then subdivided into childhood (aged ≤14 years) and adolescent (aged from 15 to ≤18 years) age series. On multivariate comparison, the Japanese pediatric PTC was characterized by a higher sex ratio (p=1.

Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort.

Background: There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.

Methods: This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13,243) during prescreening and four successive thyroid screenings.

In utero exposure to iodine-131 from Chernobyl fallout and anthropometric characteristics in adolescence.

Prenatal exposure to external radiation has been linked to growth retardation among atomic bomb survivors in adolescence. It is unclear from previous studies whether in utero exposure to internal radiation such as iodine-131 (I-131), which concentrates in the thyroid gland, has an effect on physical growth. We examined the associations between estimated thyroid gland dose from prenatal exposure to I-131 and self-reported height and weight in a cohort of 2,460 individuals exposed to radioactive fallout from the 1986 Chernobyl nuclear accident [mean I-131 dose = 72 (mGy)] and screened for thyroid diseases in adolescence.

Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the Chernobyl accident.

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto.

ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer.

Background: In their previous analysis of papillary thyroid carcinomas (PTCs) from an Ukrainian-American cohort that was exposed to iodine-131 ((131) I) from the Chernobyl accident, the authors identified RET/PTC rearrangements and other driver mutations in 60% of tumors.

Methods: In this study, the remaining mutation-negative tumors from that cohort were analyzed using RNA sequencing (RNA-Seq) and reverse transcriptase-polymerase chain reaction to identify novel chromosomal rearrangements and to characterize their relation with radiation dose.

Results: The ETS variant gene 6 (ETV6)-neurotrophin receptor 3 (NTRK3) rearrangement (ETV6-NTRK3) was identified by RNA-Seq in a tumor from a patient who received a high (131) I dose.

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.

Background: Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited.

Methods: Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria.

I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers.

Objective: To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study.

Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514).

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: cytohistopathologic correlation and accuracy of fine-needle aspiration biopsy in nodules detected during the first screening in Ukraine (1998-2000).

Background: The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA).

Factors associated with elevated serum concentrations of anti-TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian-American Cohort Study of thyroid cancer and other thyroid diseases following the Chornobyl accident.

Objectives: To examine factors associated with the prevalence of elevated anti-thyroid peroxidase antibodies (ATPO) among iodine-deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre.

Design: Subjects were members of the Ukrainian-American Cohort Study exposed to the Chornobyl accident whose (131)I thyroid dose estimates were below 0.2 Gy.

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: dose-response analysis of thyroid follicular adenomas detected during first screening in Ukraine (1998-2000).

The Chornobyl (Chernobyl) accident in 1986 exposed many individuals to radioactive iodines, chiefly (131)I, the effects of which on benign thyroid diseases are largely unknown. To investigate the risk of follicular adenoma in relation to radiation dose after Chornobyl, the authors analyzed the baseline data from a prospective screening cohort study of those exposed as children or adolescents. A stratified random sample was selected from all individuals who were younger than 18 years, had thyroid radioactivity measurements taken within 2 months after the accident, and resided in the three heavily contaminated areas in Ukraine.