Low Prevalence of RET Rearrangements (RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET) in Sporadic Papillary Thyroid Carcinomas in Taiwan Chinese

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Abstract
Somatic rearrangement of the tyrosine kinase receptor RET is restricted to papillary thyroid carcinoma (PTC). The prevalence of RET/PTC1, RET/PTC2, and RET/PTC3 has been found to vary between 0% and 20% in most series of sporadic (nonradiation-induced) PTCs analyzed by type-specific reverse transcription-polymerase chain reaction (RT-PCR) alone. However, high prevalence reported from Taiwan (6 out of 11, 55%) indicates RET rearrangement is an important genetic lesion underlying the development of PTC in Taiwan. Because the high prevalence of RET rearrangements in Chinese patients was particularly striking, we were prompted to reexamine chimeric transcripts of RET/PTC1, RET/PTC2, and RET/PTC3 using the same experimental designs in a larger number of cases in the same population. RT-PCR was performed to amplify fusion products of RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET from frozen tissue of 105 sporadic PTCs. RT-PCR was also performed with two different primer sets for RET/PTC1, RET/PTC2, and RET/PTC3 followed by Southern hybridization in the first 62 tumors. In our study, RET/PTC1, RET/PTC2, and RET/PTC3 oncogenes were found in only 7 of 105 (7%) sporadic PTCs. Of these tumors, 3 involved RET/PTC1 and 4 involved RET/PTC3. No RET/PTC2 rearrangements were observed. In the first 62 tumor samples, another two different primer sets for each rearrangement also gave concordant results. Furthermore, application of Southern hybridization in these 62 PTCs did not identify additional tumor harboring RET chimeric transcripts. We identified one tumor as having an ELKS-RET rearrangement (1 of 105, 1%). In conclusion, we detected RET rearrangements in 8 of 105 (8%) sporadic PTCs in Taiwan, a much lower prevalence than previously reported for this population but comparable to those reported in other nations using similar methodology. RET chimeric oncogenes only account for a small fraction of PTCs in Taiwan.