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Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer

Author(s): Heinz-Ulrich G. Weier | Yuko Ito | Johnson Kwan | Jan Smida | Jingly F. Weier | Ludwig Hieber | Chun-Mei Lu | Lars Lehmann | Mei Wang | Haig J. Kassabian | Hui Zeng | Benjamin O’Brien

Journal: Genes
ISSN 2073-4425

Volume: 2;
Issue: 3;
Start page: 397;
Date: 2011;
Original page

Keywords: Chernobyl | neoplastic disease | papillary thyroid cancer | translocation | molecular cytogenetics | breakpoint delineation | fluorescence in situ hybridization | bacterial artificial chromosomes

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.
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