RET/PTC rearrangements arising from a small population of papillary thyroid carcinoma cells, possible candidate for passenger mutation

RET rearrangements (RET/PTC) is a major genetic alteration in papillary thyroid carcinomas. However, the prevalence of RET/PTC differs considerably among investigators, and its impact on cancer progression has been controversial. In the current study, we applied interphase fluorescence in situ hybridization (FISH) to touch imprint cytology of 14 papillary thyroid carcinomas along with reverse-transcription polymerase chain reaction (RT-PCR) analysis. FISH DNA probes included RET locus, and PCR primers were designed targeting RET/PTC1 or RET/PTC3. Split FISH signals of RET was observed in 78.6% (11/14) of tumors. Proportions of tumor cells having split RET signals ranged from 1.8% to 19.6% (mean 9.7%) in those 11 tumors. In RT-PCR analysis, RET/PTC was found in 28.6% (4/14) of tumors. Among tumors with split RET signals, 36.4% (4/11) of tumors exhibited detectable messenger RNA of RET/PTC1 or RET/PTC3. The remaining seven tumors with split RET signals had no RET/PTCs amplicon. In conclusion, the current study disclosed that RET/PTCs occur in a small population of tumor cells in papillary thyroid carcinomas. Even though RET/PTC is a specific genetic event in the carcinomas, our results suggested the possibility of RET/PTC as passenger abnormalities rather than driver oncogenic mutation during thyroid cancer progression, warranting further studies on mechanisms and implication of RET gene instability.