Title: High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident
Author:Klugbauer S., Lengfelder E., Demidchik E.P., Rabes H.M.
Reference:Oncogene N 12, 1995, т.11, стр.2459-2467
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Title: Molecular analysis of radiation-induced thyroid carcinomas in humans
Author: Rabes, Hartmut M
Reference: International Congress Series, 1236, p.207-215, Jul 2002
doi: 10.1016/S0531-5131(01)00750-6
Keywords: Papillary thyroid carcinoma; Gene rearrangement; RET; NTRK1; Genotype/phenotype correlations
Abstract: Correlations have been found between radiation exposure and thyroid carcinoma development, particularly in children. Recent studies on a large cohort of radiation-induced papillary thyroid carcinomas (PTC) after the Chernobyl reactor accident disclosed a common type of underlying genetic alteration. A high prevalence of rearrangements of the receptor tyrosine kinase (TK) c-RET was observed, besides some rearrangements involving NTRK1. Radiation-induced RET rearrangements in PTC consist most frequently of fusions to the H4 gene (RET/PTC1) or to the ELE1 (ARA70) gene (RET/PTC3). Both fusions are formed by balanced paracentric inversions on chromosome 10. An analysis of the fused genes in ELE1/RET rearrangements revealed DNA double-strand breaks spread over a distance of about 2.3 kb in two introns and the interposed exon of ELE1, exon 11 and intron 11 of RET, without significant clustering in these parts of the genes. Topoisomerase I sites were found exactly at or in close vicinity to all breakpoints, suggesting a role for this enzyme in formation of DNA strand breaks or inversions. The genes fuse at short regions of sequence homology and short direct or inverted repeats (microhomology-mediated DNA end joining). A minority of PTC cases contain novel types of RET rearrangement, with RIα, GOLGA2, HTIF, HTIF homolog, RFG8, ELKS, KTN1 and PCM-1 as the 5′-fused genes. These novel types of gene fusions are formed by interchromosomal translocation. The formation of these rare types of rearrangement seems to be highly related to radiation as they have rarely been found in sporadic PTC. All RET gene fusions seem to act similarly on RET function: The strict physiological control of RET TK activity is suspended through constitutive activation by 5′-fused parts of genes containing coiled-coil domains with dimerization potential. RET expression in thyrocytes, which under normal conditions, lack RET TK activity apparently triggers clonal expansion and early invasion of the affected cells. RET-fused genes, some of which are transcriptional coactivators, are important determinators of the peculiar phenotype of the tumour and for its clinical course. This is most significant in RET/PTC3 rearrangements with ELE1 as the RET-fused gene: this type of rearrangement leads more often to the phenotype of a solid variant of PTC, and to rapid tumour development and early lymph node metastasis. Up to now, no other genetic aberration has more frequently been observed in PTC than RET rearrangement, thus suggesting that RET rearrangement represents a genetic marker lesion of radiation history in the development of a PTC.
URL: http://www.sciencedirect.com/science/article/pii/S0531513101007506
Author: Rabes, Hartmut M
Reference: International Congress Series, 1234, p.193-200, May 2002
doi: 10.1016/S0531-5131(01)00608-2
Keywords: Papillary thyroid carcinoma; Gene rearrangement; DNA breakpoints; Irradiation; RET
Abstract: Papillary thyroid carcinomas (PTC) developed with a high incidence in children and young adults who had been exposed to radioactive fallout in contaminated regions of Belarus after the Chernobyl reactor accident. They are informative for a molecular genetic analysis of radiation-induced PTC. In contrast to spontaneous PTC, a high prevalence of gene aberrations was found with rearrangements of the receptor tyrosine kinase gene RET in the majority of cases and a few NTRK1 rearrangements. In the rearranged form of RET, the transmembrane and extracellular parts are replaced by regulatory units of other genes….
URL: http://www.sciencedirect.com/science/article/pii/S0531513101006082
Title: Activated RET oncogene in thyroid cancers of children from areas contaminated by Chernobyl accident
Author: Takashi lto / Toshio Seyama / Iwamoto, S. / Terumi Mizuno / Tronko, NikolaiD. / Komissarenko, IgorV. / Cherstovoy, EbgenyD. / (…) / Mitoshi Akiyama
Reference: The Lancet, 344 (8917), p.259, Jul 1994
doi: 10.1016/S0140-6736(94)93024-4
Abstract: …United Kingdom SiR-Thyroid cancer is recognised as a…been an increase in thyroid cancers among children…contaminated by the Chernobyl accident.2 On the…Ruchti C. Williams D. Thyroid cancer after Chernobyl Nature 359 1992 21…
URL: http://www.sciencedirect.com/science/article/pii/S0140673694930244
Title: RET oncogene puzzle in Chernobyl thyroid tumours
Author: Bonn, Dorothy
Reference: The Lancet, 347 (9009), p.1176, Apr 1996
doi: 10.1016/S0140-6736(96)90626-1
Abstract: …MEDICINE RET oncogene puzzle in Chernobyl thyroid tumours Dorothy Bonn In 1990, 4 years after the Chernobyl nuclear reactor acci- dent in…1986, came the first reports of thyroid cancer in children who had been living…
URL: http://www.sciencedirect.com/science/article/pii/S0140673696906261
Title: Thyroid cancer
Author: Gimm, Oliver
Reference: Cancer Letters, 163 (2), p.143-156, Feb 2001
doi: 10.1016/S0304-3835(00)00697-2
Keywords: Papillary; Follicular; Undifferentiated; Medullary; ras; RET; TRK; PTEN; p53; Diagnosis; Management
Abstract: …process [33] . Thyroid cancer is considered to be a…Actually, about 10% of all thyroid cancers are diagnosed in this age group. The Chernobyl disaster from 1986 has…fallout on the incidence of thyroid cancer, in particular PTC in…
URL:http://www.sciencedirect.com/science/article/pii/S0304383500006972
Title: Molecular pathology of thyroid cancer: diagnostic and clinical implications
Author: Fagin, James A. / Mitsiades, Nicholas
Reference: Best Practice & Research Clinical Endocrinology & Metabolism, 22 (6), p.955-969, Dec 2008
doi: 10.1016/j.beem.2008.09.017
Keywords: thyroid cancer; pathogenesis; oncogene; RET; BRAF; RAS; molecular diagnostics; PTEN; PI3 kinase
Abstract: …receptor (RET/PTC) in thyroid cells that are constitutively…a very early event in thyroid cancer development. Thus…11 or RET/PTC3 12 in thyroid cells. In addition…characteristics. In post-Chernobyl pediatric cancers RET…
URL: http://www.sciencedirect.com/science/article/pii/S1521690X08001127
Author: Nakashima, Masahiro / Takamura, Noboru / Namba, Hiroyuki / Saenko, Vladimir A. / Suzuki, Keiji / Meirmanov, Serik / Hayashi, Tomayoshi / Sekine, Ichiro
Reference: International Congress Series, 1299, p.251-255, Feb 2007
doi: 10.1016/j.ics.2006.09.002
Keywords: Thyroid cancer; RET oncogene; Genomic instability; 53BP1; Radiation; Interphase FISH
Abstract: RET oncogene rearrangement is a well-known molecular alteration observed in papillary thyroid cancer (PTC). RET rearrangement is the commonest oncogenic alterations in Chernobyl-related PTC; nearly all to RET/PTC1 or RET/PTC3, resulting from paracentric inversion of chromosome 10. Other less common variants, usually forming as a result of interchromosomal translocation, occur in an extremely limited number of cases….
URL:http://www.sciencedirect.com/science/article/pii/S0531513106006182