A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

Port, Matthias; Boltze, Carsten; Wang, Y.; Röper, Barbara; Meineke, Viktor; Abend, Michael

doi:10.1667/rr0968.1

Cited by 51 publications

(39 citation statements)

References 60 publications

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“…Furthermore, this signature allows for classifying tumors from Belarus and Ukraine as either sporadic or occurring in highly contaminated subjects during the Chernobyl accident (43). These data confirm previous studies (44)(45)(46)(47) and suggest that radiation-induced tumors may have some specific molecular characteristics, but this should be confirmed on a larger series of tumors.…”

Section: Radiation-induced Thyroid Cancersupporting

confidence: 85%

Radiation exposure and thyroid cancer: a review

Iglesias

Schmidt

Ghuzlan

et al. 2017

Arch. Endocrinol. Metab.

156

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The association between radiation exposure and the occurrence of thyroid cancer has been well documented, and the two main risk factors for the development of a thyroid cancer are the radiation dose delivered to the thyroid gland and the age at exposure. The risk increases after exposure to a mean dose of more than 0.05-0.1 Gy (50-100mGy). The risk is more important during childhood and decreases with increased age at exposure, being low in adults. After exposure, the minimum latency period before the appearance of thyroid cancers is 5 to 10 years. Papillary carcinoma (PTC) is the most frequent form of thyroid carcinoma diagnosed after radiation exposure, with a higher prevalence of the solid subtype in young children with a short latency period and of the classical subtype in cases with a longer latency period after exposure. Molecular alterations, including intrachromosomal rearrangements, are frequently found. Among them, RET/PTC rearrangements are the most frequent. Current research is directed on the mechanism of genetic alterations induced by radiation and on a molecular signature that can identify the origin of thyroid carcinoma after a known or suspected exposure to radiation. Arch Endocrinol Metab. 2017;61(2):180-7.

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Section: Radiation-induced Thyroid Cancersupporting

confidence: 85%

Radiation exposure and thyroid cancer: a review

Iglesias

Schmidt

Ghuzlan

et al. 2017

Arch. Endocrinol. Metab.

156

View full text Add to dashboard Cite

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“…Previously published studies suggesting a radiation gene expression signature in post-Chernobyl cases (24,25) therefore need careful interpretation, because the nonirradiated comparator population is usually drawn from an adult series of PTCs instead of childhood cases. We therefore aimed to identify radiation-specific CNAs in PTCs by directly comparing agematched tumor cohorts, for which the main difference between them was exposure to radioiodine fallout.…”

Section: Discussionmentioning

confidence: 99%

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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“…On the other hand, the difference could, in part, reflect specific changes in gene expression in radiation-induced OS, since recent microarray studies have reported that spontaneous and radiation-induced cancers are distinguishable based on gene expression patterns even though most gene expressions are common to both cancers. 50,51 However, future studies will be required to determine whether there are specific changes in gene expression in OS induced by ionizing radiation.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of alpha‐radiation‐induced rat osteosarcomas: Identification of dysregulated genes involved in radiation‐induced tumorigenesis of bone

Daino

Ugolin

Altmeyer-Morel

et al. 2009

Intl Journal of Cancer

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To better understand the molecular basis of radiation-induced osteosarcoma (OS), we performed global gene expression profiling of rat OS tumors induced by the bone-seeking alpha emitter 238 Pu, and the expression profiles were compared with those of normal osteoblasts (OB). The expressions of 72 genes were significantly differentially expressed in the tumors related to OB. These included genes involved in the cell adhesion (e.g., Podxl, Col18a1, Cd93, Emcn and Vcl), differentiation, developmental processes (e.g., Hhex, Gata2, P2ry6, P2rx5, Cited2, Osmr and Igsf10), tumorsuppressor function (e.g., Nme3, Blcap and Rrm1), Src tyrosine kinase signaling (e.g., Hck, Shf, Arhgap29, Cttn and Akap12), and Wnt/b-catenin signaling (e.g., Fzd6, Lzic, Dkk3 and Ctnna1) pathways. Expression changes of several genes were validated by quantitative real-time RT-PCR analysis. Notably, all of the identified genes involved in the Wnt/b-catenin signaling pathway were known or proposed to be negative regulators of this pathway and were downregulated in the tumors, suggesting the activation of bcatenin in radiation-induced OS. By using immunohistochemical and immunoblot analyses, constitutive activation of the Wnt/b-catenin signaling pathway in the tumors was confirmed by observing nuclear and/or cytoplasmic localization of b-catenin and a decrease in its inactive (phosphorylated) form. Furthermore, we found a significant reduction in the levels of glycogen synthase kinase 3b (GSK-3b) protein in the tumors relative to OB. Taken together, these findings provide new insights into the molecular basis of radiation-induced OS. ' UICCKey words: osteosarcoma; osteoblast; ionizing radiation; carcinogenesis; transcriptome Osteosarcoma (OS) is the most common primary tumor of bone in children and adolescents. The peak incidence of OS occurs in the second decade of life, with an additional smaller peak in the elderly population. This tumor is highly aggressive and is thought to arise primarily from osteoblasts (OB), boneforming cells. An increased risk for developing OS is known to be associated with some genetic disorders, such as hereditary retinoblastoma and Li-Fraumeni syndrome with germline mutations in the retinoblastoma (RB1) and TP53 genes, respectively. 1,2 In agreement with this, abnormalities of genes involved in the RB1 and TP53 tumor-suppressor pathways are often found in OS. 3,4 On the other hand, the association between ionizing radiation and the subsequent development of OS has been well documented in prior studies. For example, OS is known as one of the most frequent secondary malignant neoplasms occurring within the radiation field in patients, especially with retinoblastoma, treated with radiation therapy. 1,5 The risk of OS has been reported to be increased following the internal exposure to bone-seeking radioisotopes from occupational or medicinal use. 6-8 Interestingly, some studies have revealed the genetic and cytogenetic changes in radiation-induced OS and suggested the presence of additional tumor-associated genes. ...

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A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

Cited by 51 publications

References 60 publications

Radiation exposure and thyroid cancer: a review

Radiation exposure and thyroid cancer: a review

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

Gene expression profiling of alpha‐radiation‐induced rat osteosarcomas: Identification of dysregulated genes involved in radiation‐induced tumorigenesis of bone

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