PMID- 15356021 OWN - NLM STAT- MEDLINE DCOM- 20041007 LR - 20120604 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 89 IP - 9 DP - 2004 Sep TI - Heterogeneity in the distribution of RET/PTC rearrangements within individual post-Chernobyl papillary thyroid carcinomas. PG - 4272-9 AB - The nuclear disaster that occurred in Chernobyl in 1986 offered the unique opportunity to study the molecular genetics of one human tumor type, papillary carcinoma of the thyroid gland, associated with a specific etiology. We have analyzed RET rearrangements in post-Chernobyl papillary thyroid carcinomas (n = 29), follicular thyroid adenomas (n = 2), and follicular thyroid carcinoma (n = 1) by interphase fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue sections. Paraffin sections were microdissected before use to ensure that only tumor was present. Cell nuclei were scored for the presence of a split FISH signal (separated red and green signal) in addition to an overlapping signal. Only cells with either two overlapping signals or one split and one overlapping signal were counted to ensure that only complete cell nuclei had been scored. In total, 23 of 32 cases (72%) showed RET rearrangements diagnosed by FISH interphase analysis. In all cases, the tumors were composed of a mixture of cells with and without ret rearrangement on FISH. In some cases, this distribution was clearly nonrandom because clustering of rearranged cells was detected within the same tumor nodule. Accordingly, only 31% of the cases positive for rearrangement on FISH also scored positive using RT-PCR. These findings suggest that because RET/PTC rearrangements are not present in a majority of tumor cells, either a fraction of post-Chernobyl papillary thyroid tumors are of multiclonal origin, or ret rearrangement is a later, subclonal event. FAU - Unger, Kristian AU - Unger K AD - GSF-Forschungszentrum fur Umwelt und Gesundheit GmbH, Institute of Molecular Radiobiology, Ingolstadter Landstrasse 1, D-85764 Neuherberg, Germany. FAU - Zitzelsberger, Horst AU - Zitzelsberger H FAU - Salvatore, Giuliana AU - Salvatore G FAU - Santoro, Massimo AU - Santoro M FAU - Bogdanova, Tatjana AU - Bogdanova T FAU - Braselmann, Herbert AU - Braselmann H FAU - Kastner, Peter AU - Kastner P FAU - Zurnadzhy, Lyudmilla AU - Zurnadzhy L FAU - Tronko, Nikolay AU - Tronko N FAU - Hutzler, Peter AU - Hutzler P FAU - Thomas, Gerry AU - Thomas G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Oncogene Proteins) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret) RN - EC 2.7.10.1 (RET protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM CIN - J Clin Endocrinol Metab. 2004 Sep;89(9):4264-6. PMID: 15356019 MH - Adolescent MH - Carcinoma, Papillary/*genetics MH - Child MH - Female MH - *Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Neoplasms, Radiation-Induced/*genetics MH - Oncogene Proteins/*genetics MH - *Power Plants MH - Proto-Oncogene Proteins c-ret MH - *Radioactive Hazard Release MH - Receptor Protein-Tyrosine Kinases/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thyroid Neoplasms/*genetics MH - Ukraine EDAT- 2004/09/10 05:00 MHDA- 2004/10/08 09:00 CRDT- 2004/09/10 05:00 PHST- 2004/09/10 05:00 [pubmed] PHST- 2004/10/08 09:00 [medline] PHST- 2004/09/10 05:00 [entrez] AID - 89/9/4272 [pii] AID - 10.1210/jc.2003-031870 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2004 Sep;89(9):4272-9. doi: 10.1210/jc.2003-031870.