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Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer
Life Sciences Division, E.O. Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
National Institute of Science and Technology Policy (NISTEP), Ministry of Education, Culture, Sports, Science and Technology, Tokyo 100-0005, Japan
Clinical Cooperation Group Osteosarcoma, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
Clinical Labs–Cytogenetics, University of California, 185 Berry Street Suite 290, San Francisco, CA 94143-0100, USA
Department of Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr.1, Neuherberg 85764, Germany
Department of Chemical and Materials Engineering, National Chin-Yi University of Technology, No.35, Lane 215, Section 1, Chungshan Road, Taiping City, Taichung 411, Taiwan
Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany
Department of Diabetes, City of Hope, 1500 Duarte Road, Duarte, CA 91010-3012, USA
William Harvey Research Institute, Translational Medicine and Therapeutics, Barts and The London School of Medicine, Charterhouse Square, London, EC1M 6BQ, UK
Department of Anesthesiology, German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
* Author to whom correspondence should be addressed.
Received: 23 April 2011; in revised form: 23 May 2011 / Accepted: 16 June 2011 / Published: 28 June 2011
Abstract: Recurrent translocations are well known hallmarks of many human solid tumors and hematological disorders, where patient- and breakpoint-specific information may facilitate prognostication and individualized therapy. In thyroid carcinomas, the proto-oncogenes RET and NTRK1 are often found to be activated through chromosomal rearrangements. However, many sporadic tumors and papillary thyroid carcinomas (PTCs) arising in patients with a history of exposure to elevated levels of ionizing irradiation do not carry these known abnormalities. We developed a rapid scheme to screen tumor cell metaphase spreads and identify candidate genes of tumorigenesis and neoplastic progression for subsequent functional studies. Using a series of overnight fluorescence in situ hybridization (FISH) experiments with pools comprised of bacterial artificial chromosome (BAC) clones, it now becomes possible to rapidly refine breakpoint maps and, within one week, progress from the low resolution Spectral Karyotyping (SKY) maps or Giemsa-banding (G-banding) karyotypes to fully integrated, high resolution physical maps including a list of candiate genes in the critical regions.
Keywords: Chernobyl; neoplastic disease; papillary thyroid cancer; translocation; molecular cytogenetics; breakpoint delineation; fluorescence in situ hybridization; bacterial artificial chromosomes
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Weier, H.-U.; Ito, Y.; Kwan, J.; Smida, J.; Weier, J.F.; Hieber, L.; Lu, C.-M.; Lehmann, L.; Wang, M.; Kassabian, H.J.; Zeng, H.; O’Brien, B. Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer. Genes 2011, 2, 397-419.
Weier H-U, Ito Y, Kwan J, Smida J, Weier JF, Hieber L, Lu C-M, Lehmann L, Wang M, Kassabian HJ, Zeng H, O’Brien B. Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer. Genes. 2011; 2(3):397-419.
Weier, Heinz-Ulrich G.; Ito, Yuko; Kwan, Johnson; Smida, Jan; Weier, Jingly F.; Hieber, Ludwig; Lu, Chun-Mei; Lehmann, Lars; Wang, Mei; Kassabian, Haig J.; Zeng, Hui; O’Brien, Benjamin. 2011. "Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer." Genes 2, no. 3: 397-419.