タグ「Gene rearrangement」
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
Title: Rearrangements of NTRK1 gene in papillary thyroid carcinoma
Author: Greco, A. / Miranda, C. / Pierotti, M.A.
Reference: Molecular and Cellular Endocrinology, 321 (1), p.44-49, May 2010
doi: 10.1016/j.mce.2009.10.009
Keywords: NTRK1; Gene rearrangement; Papillary thyroid tumor
Abstract: …starting from papillary thyroid tumor DNA. Transforming…isolated from papillary thyroid tumors are reported in Table…radioiodine released from the Chernobyl reactor a high rate of…event in the process of thyroid carcinogenesis. Transgenic…penetrance of thyroid cancer and shortens the latency…
URL: http://www.sciencedirect.com/science/article/pii/S0303720709005565
Title: Rearrangements of NTRK1 gene in papillary thyroid carcinoma
Author: Greco, A. / Miranda, C. / Pierotti, M.A
Reference: Molecular and Cellular Endocrinology, 321 (1), p.44-49, May 2010
doi: 10.1016/j.mce.2009.10.009
Keywords: NTRK1; Gene rearrangement; Papillary thyroid tumor
Abstract: …starting from papillary thyroid tumor DNA. Transforming…isolated from papillary thyroid tumors are reported in Table…radioiodine released from the Chernobyl reactor a high rate of…event in the process of thyroid carcinogenesis. Transgenic…penetrance of thyroid cancer and shortens the latency…
URL:http://www.sciencedirect.com/science/article/pii/S0303720709005565
Title: Molecular rearrangements in papillary thyroid carcinomas
Author: Zitzelsberger, Horst / Bauer, Verena / Thomas, Gerry / Unger, Kristian
Reference: Clinica Chimica Acta, 411 (5-6), p.301-308, Mar 2010
doi: 10.1016/j.cca.2009.11.028
Keywords: Papillary thyroid carcinoma; Gene rearrangement; Chromosome aberrations; Genetic heterogeneity
Abstract: …post-Chernobyl papillary thyroid carcinomas some researchers…radiation-associated thyroid carcinomas. However…contrast to the post-Chernobyl tumours, radiation-associated thyroid tumours either originated…in sporadic thyroid cancer in children [40…
URL: http://www.sciencedirect.com/science/article/pii/S0009898109006172
Title: Gene rearrangements in thyroid carcinomas after irradiation during childhood: lessons from the Chernobyl reactor accident
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: Post-Chernobyl thyroid carcinoma in children
Author: Leenhardt, Laurence / Aurengo, André
Reference: Best Practice & Research Clinical Endocrinology & Metabolism, 14 (4), p.667-677, Dec 2000
doi: 10.1053/beem.2000.0109
Keywords: Chernobyl; accidents, radiation; children, thyroid carcinoma; thyroid neoplasms/*genetics; carcinoma, papillary/*genetics; molecular sequence data; mutation/*genetics; gene rearrangement; Ukraine; Belarus
Abstract: The dramatic increase in childhood thyroid carcinoma observed in Belarus and Ukraine as early as 4 years after the Chernobyl nuclear accident, is well recognized as being a consequence of exposure to radioactive iodine fallout. Uncertainties persist concerning the contamination and the dosimetric data. Thyroid nodule, cervical lymph nodes or systematic ultrasound thyroid screening in exposed children led to the diagnosis….
URL: http://www.sciencedirect.com/science/article/pii/S1521690X0090109X
Title: Molecular epidemiology of childhood thyroid cancer around Chernobyl
Author: Yamashita, Shunichi / Shibata, Yoshisada / Namba, Hiroyuki / Takamura, Noboru / Saenko, Vladimir,
Reference: International Congress Series, 1236, p.201-205, Jul 2002
doi: 10.1016/S0531-5131(01)00855-X
Keywords: Chernobyl; Screening ; Thyroid cancer; Gene rearrangement; Signal transduction
Abstract: …The comparative study of thyroid diseases demonstrates the likelihood of short-lived radioactive iodine on thyroid cancer in the children born before the Chernobyl accident. Next, at the standpoint of recent molecular analysis of thyroid carcinogenesis, many reports now indicate evidence of a high incidence of ret/PTC gene rearrangement in childhood thyroid cancer tissues. Besides ret/PTC gene rearrangement, the disturbance of the response of intracellular signal transduction to radiation exposure is also important in thyroid cells, and results demonstrate that radiation exposure could cause abnormal thyroid cell proliferation specifically through constitutive activation of intracellular target molecules via membrane lipid breakdown, and subsequently disturb the apoptosis-prone pathway. …Therefore, the late effect of radiation, even in the lower dose on the human thyroid glands, should be monitored carefully for the radiation-sensitive vulnerable group for a longer period, especially around Chernobyl.
URL: http://www.sciencedirect.com/science/article/pii/S053151310100855X
