PMID- 22328910 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 1876-3901 (Print) IS - 1876-3901 (Electronic) VI - 2 DP - 2010 TI - 'Chromosomal Rainbows' Detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors. PG - 13-22 AB - Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'- end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners.We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabasepair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding techniques for fine mapping of breakpoints in papillary thyroid cancer (PTC). FAU - O'Brien, Benjamin AU - O'Brien B AD - Life Sciences Division, E.O. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. FAU - Jossart, Gregg H AU - Jossart GH FAU - Ito, Yuko AU - Ito Y FAU - Greulich-Bode, Karin M AU - Greulich-Bode KM FAU - Weier, Jingly F AU - Weier JF FAU - Munne, Santiago AU - Munne S FAU - Clark, Orlo H AU - Clark OH FAU - Weier, Heinz-Ulrich G AU - Weier HU LA - eng GR - R21 CA123370-02/CA/NCI NIH HHS/United States GR - R01 CA136685/CA/NCI NIH HHS/United States GR - R21 CA123370/CA/NCI NIH HHS/United States GR - R01 HD045736/HD/NICHD NIH HHS/United States GR - R01 CA136685-03/CA/NCI NIH HHS/United States GR - R01 HD045736-03/HD/NICHD NIH HHS/United States GR - R01 CA080792-01A2/CA/NCI NIH HHS/United States PT - Journal Article PL - Netherlands TA - Open Cell Signal J JT - The open cell signaling journal JID - 101555349 PMC - PMC3276079 MID - NIHMS265714 EDAT- 2010/01/01 00:00 MHDA- 2010/01/01 00:01 PMCR- 2012/02/09 CRDT- 2012/02/14 06:00 PHST- 2012/02/14 06:00 [entrez] PHST- 2010/01/01 00:00 [pubmed] PHST- 2010/01/01 00:01 [medline] PHST- 2012/02/09 00:00 [pmc-release] AID - 10.2172/1011038 [doi] PST - ppublish SO - Open Cell Signal J. 2010;2:13-22. doi: 10.2172/1011038.