RET rearrangements in radiation-induced papillary thyroid carcinomas: high prevalence of topoisomerase I sites at breakpoints and microhomology-mediated end joining in ELE1 and RET chimeric genes

Genomics
S KlugbauerH M Rabes

Abstract

Children exposed to radioactive iodine after the Chernobyl reactor accident frequently developed papillary thyroid carcinomas (PTC). The predominant molecular lesions in these tumors are rearrangements of the RET receptor tyrosine kinase gene. Various types of RET rearrangements have been described. More than 90% of PTC with RET rearrangement exhibit a PTC1 or PTC3 type of rearrangement with an inversion of the H4 or ELE1 gene, respectively, on chromosome 10. To obtain closer insight into the mechanisms underlying PTC3 inversions, we analyzed the genomic breakpoints of 22 reciprocal and 4 nonreciprocal ELE1 and RET rearrangements in 26 post-Chernobyl tumor samples. In contrast to previous assumptions, an accumulation of breakpoints at the two Alu elements in the ELE1 sequence was not observed. Instead, breakpoints are distributed in the affected introns of both genes without significant clustering. When compared to the corresponding wildtype sequences, the majority of breakpoints (92%) do not contain larger deletions or insertions. Most remarkably, at least one topoisomerase I site was found exactly at or in close vicinity to all breakpoints, indicating a potential role for this enzyme in the formation of DNA strand breaks and/...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M A PierottiA Fusco
Jun 24, 1988·Nucleic Acids Research·J R Spitzner, M T Muller
Jan 1, 1985·Annual Review of Biochemistry·J C Wang
Oct 1, 1985·Molecular and Cellular Biology·D B RothJ H Wilson
Jan 1, 1988·Progress in Nucleic Acid Research and Molecular Biology·J F Ward
Sep 5, 1981·Journal of Molecular Biology·P L DeiningerC W Schmid
Sep 1, 1994·Genes, Chromosomes & Cancer·F MinolettiI Bongarzone
Dec 1, 1995·Human Molecular Genetics·P A SmanikS M Jhiang
Apr 1, 1996·Molecular and Cellular Biology·J Zhu, R H Schiestl
Jan 1, 1996·Annual Review of Biochemistry·J C Wang
Aug 11, 1998·Trends in Biochemical Sciences·P Baumann, S C West
Sep 5, 1998·Mutation Research·P E Bryant
Nov 12, 1998·Trends in Biochemical Sciences·S E Critchlow, S P Jackson
Nov 20, 1998·Toxicology Letters·P Pfeiffer
Dec 23, 1998·Trends in Cell Biology·R KanaarD C van Gent
Jan 5, 1999·European Journal of Biochemistry·B GöttlichP Pfeiffer
Feb 6, 1999·International Journal of Cancer. Journal International Du Cancer·J SmidaM Bauchinger
Feb 23, 1999·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·H M Rabes, S Klugbauer
Mar 13, 1999·International Journal of Cancer. Journal International Du Cancer·C BeimfohrH M Rabes
Apr 10, 1999·Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie·J Thacker
May 5, 1999·Nature·J E Haber
May 8, 2001·Medical and Pediatric Oncology·H M Rabes

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Citations

Jul 1, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Adel AssaadJennifer L Hunt
Sep 4, 2009·Thyroid : Official Journal of the American Thyroid Association·Ana Paula Zen Petisco FioreEdna Teruko Kimura
Jul 5, 2012·Journal of Thyroid Research·Laura W DillonYuh-Hwa Wang
Jul 24, 2010·Endocrine Reviews·Bridget SinnottArthur B Schneider
Sep 17, 2013·PloS One·Laura W DillonYuh-Hwa Wang
Jul 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicolas VogtBernard Malfoy
Apr 12, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Tatsuji MizukamiTakashi Kohno
May 7, 2002·International Journal of Cancer. Journal International Du Cancer·Ioannis PanagopoulosNils Mandahl
Sep 22, 2009·Molecular and Cellular Endocrinology·Manoj GandhiYuri E Nikiforov
Aug 28, 2009·Cancer Letters·Elisavet GatzidouStamatios Theocharis
Aug 25, 2006·Nature Clinical Practice. Endocrinology & Metabolism·Arthur B Schneider, David H Sarne
Aug 13, 2013·Molecular and Cellular Endocrinology·Dang Vu-Phan, Ronald J Koenig
May 8, 2001·Medical and Pediatric Oncology·H M Rabes
Apr 25, 2007·Nature Clinical Practice. Endocrinology & Metabolism·Shunichi Yamashita, Vladimir Saenko
Jan 25, 2003·Human Genetics·Clesson TurnerLeslie G Biesecker
Apr 25, 2020·Genes·Massimo SantoroFrancesca Carlomagno
Oct 14, 2020·Plant Biotechnology Journal·Tien Van VuJae-Yean Kim

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