Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.
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ABSTRACT:
SUBMITTER: Morton LM
PROVIDER: S-EPMC9022889 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionising radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors.
| S-EPMC6065115 | biostudies-literature
Project description:Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident
| PRJNA324142 | ENA
Project description:BackgroundThe 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 131I ("radiogenic" cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to 131I ("sporadic" cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual 131I thyroid dose.MethodsThe study included 301 radiogenic and 194 sporadic PTCs. According to age at surgery, patients were subdivided into children (?14 years old), adolescents (15-18 years old), and adults (19-28 years old). Statistical analyses included univariate tests and multivariable logistic regression within and across the age subgroups. Analyses of morphological features related to 131I doses were conducted among exposed patients on categorical and continuous scales controlling for sex and age.ResultsAmong children, radiogenic PTC displayed a significantly higher frequency of tumors with a dominant solid growth pattern, intrathyroidal spread, extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adolescents more frequently displayed extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adults more frequently had intrathyroidal spread and extrathyroidal extension. The frequency of PTC with dominant papillary pattern and oxyphilic cell metaplasia was significantly lower in radiogenic compared to sporadic tumors for all age groups. Manifestations of tumor aggressiveness were most frequent in children compared to adolescents and adults regardless of etiology.ConclusionsRadiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.
| S-EPMC6112184 | biostudies-literature
Project description:One of the major consequences of the 1986 Chernobyl reactor accident was a dramatic increase in papillary thyroid carcinoma (PTC) incidence, predominantly in patients exposed to the radioiodine fallout at young age. The present study is the first on genomic copy number alterations (CNAs) of PTCs of the Ukrainian-American cohort (UkrAm) generated by array comparative genomic hybridization (aCGH). Unsupervised hierarchical clustering of CNA profiles revealed a significant enrichment of a subgroup of patients with female gender, long latency (>17 years) and negative lymph node status. Further, we identified single CNAs that were significantly associated with latency, gender, radiation dose and BRAF V600E mutation status. Multivariate analysis revealed no interactions but additive effects of parameters gender, latency and dose on CNAs. The previously identified radiation-associated gain of the chromosomal bands 7q11.22-11.23 was present in 29% of cases. Moreover, comparison of our radiation-associated PTC data set with the TCGA data set on sporadic PTCs revealed altered copy numbers of the tumor driver genes NF2 and CHEK2. Further, we integrated the CNA data with transcriptomic data that were available on a subset of the herein analyzed cohort and did not find statistically significant associations between the two molecular layers. However, applying hierarchical clustering on a 'BRAF-like/RAS-like' transcriptome signature split the cases into four groups, one of which containing all BRAF-positive cases validating the signature in an independent data set.
| S-EPMC4635667 | biostudies-literature
Project description:After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers.
| S-EPMC4399027 | biostudies-literature
Project description:The U.S. National Cancer Institute, in collaboration with the Belarusian Ministry of Health, is conducting a study of thyroid cancer and other thyroid diseases in a cohort of about 12,000 persons who were exposed to fallout from the Chernobyl accident in April 1986. The study subjects were 18 years old or younger at the time of exposure and resided in Belarus in the most contaminated areas of the Gomel and Mogilev Oblasts, as well as in the city of Minsk. All cohort members had at least one direct thyroid measurement made in April-June 1986. Individual data on residential history, consumption of milk, milk products and leafy vegetables as well as administration of stable iodine were collected for all cohort members by means of personal interviews conducted between 1996 and 2007. Based on the estimated (131)I activities in the thyroids, which were derived from the direct thyroid measurements, and on the responses to the questionnaires, individual thyroid doses from intakes of (131)I were reconstructed for all cohort members. In addition, radiation doses to the thyroid were estimated for the following minor exposure pathways: (a) intake of short-lived (132)I, (133)I and (132)Te by inhalation and ingestion; (b) external irradiation from radionuclides deposited on the ground; and (c) ingestion intake of (134)Cs and (137)Cs. Intake of (131)I was the major pathway for thyroid exposure; its mean contribution to the thyroid dose was 92%. The thyroid doses from (131)I intakes varied from 0.5 mGy to almost 33 Gy; the mean was estimated to be 0.58 Gy, while the median was 0.23 Gy. The reconstructed doses are being used to evaluate the risk of thyroid cancer and other thyroid diseases in the cohort.
| S-EPMC3682838 | biostudies-literature
Project description:ImportanceTo our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.ObjectiveTo study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.Design, setting, and participantsThis was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.Main outcomes and measuresFor analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.ResultsOf the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.Conclusions and relevanceThis cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.
| S-EPMC10436126 | biostudies-literature
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid
2007-07-12 | GSE3950 | GEO
Project description:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.
| S-EPMC4243044 | biostudies-literature
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid thyroid papillary cancer vs. patient-matched adjacent nontumor thyroid tissues. -14 tumors from France -12 tumors from Ukraine
2007-07-11 | E-GEOD-3950 | biostudies-arrayexpress