Chromosomal imbalances and RET rearrangements in radiation-induced thyroid tumours

H.E. Richter, PhD

AIM: The investigation of radiation-associated papillary thyroid tumours from children exposed to the radioactive fallout of Chernobyl in 1986 and of control tumours from Munich by CGH (Comparative Genomic Hybridization) and analysis of RET rearrangements should provide indications for molecular cytogenetic mechanisms in radiocarcinogenesis. METHOD: Frozen and microdissected paraffin-embedded tissue were used for CGH analysis. Ligation-Mediated PCR was performed for amplification of whole genomic tumour DNA. Simultaneously the DNA of all samples were analysed by RT-PCR for rearrangements of the RET proto-oncogene (RET/PTC1, RET/PTC3, TK domain). In cases where the RT-PCR amplification was insufficient hybridizations of PCR-products with radioactively labeled oligonucleotide probes were performed. RESULTS: The CGH analyses showed chromosomal imbalances in 23% (8 of 35) of the childhood tumours, for the control group of Munich we detected copy number changes in 5/8 cases. Rearrangements of the proto-oncogene RET were detected in addition to chromosomal imbalances in particular cases. CONCLUSIONS: A subset of radiation-induced thyroid tumours with rearranged forms of the RET proto-oncogene additionally showed chromosomal imbalances detected by CGH indicating an involvement of other genes in the carcinogenic process.

KEY WORDS: childhood tumours, radiocarcinogenesis, CGH (Comparative Genomic Hybridization).

For more information, contact richter@gsf.de

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.

http://www.cancerprev.org/Journal/Issues/26/101/992/4209