Liu Rue-Tsuan, Chou Fong-Fu, Wang Chih-Hui, Lin Chang-Lin, Chao Fang-Ping, Chung Jui-Chen, Huang Chao-Cheng, Wang Pei-Wen, Cheng Jiin-Tsuey
Division of Metabolism, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC.
Thyroid. 2005 Apr;15(4):326-35. doi: 10.1089/thy.2005.15.326.
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.
酪氨酸激酶受体RET的体细胞重排仅限于甲状腺乳头状癌（PTC）。在大多数仅通过型特异性逆转录-聚合酶链反应（RT-PCR）分析的散发性（非辐射诱导）PTC系列中，RET/PTC1、RET/PTC2和RET/PTC3的发生率在0%至20%之间变化。然而，台湾报道的高发生率（11例中有6例，55%）表明RET重排是台湾PTC发生的重要遗传病变。由于中国患者中RET重排的高发生率尤为显著，我们促使在同一人群中对更多病例使用相同的实验设计重新检查RET/PTC1、RET/PTC2和RET/PTC3的嵌合转录本。对105例散发性PTC的冷冻组织进行RT-PCR，以扩增RET/PTC1、RET/PTC2、RET/PTC3和ELKS-RET的融合产物。对RET/PTC1、RET/PTC2和RET/PTC3也使用两种不同的引物组进行RT-PCR，然后在前62例肿瘤中进行Southern杂交。在我们的研究中，105例散发性PTC中仅7例（7%）发现了RET/PTC1、RET/PTC2和RET/PTC3癌基因。在这些肿瘤中，3例涉及RET/PTC1，4例涉及RET/PTC3。未观察到RET/PTC2重排。在前62例肿瘤样本中，每种重排的另外两种不同引物组也给出了一致的结果。此外，在这62例PTC中应用Southern杂交未发现其他携带RET嵌合转录本的肿瘤。我们鉴定出1例肿瘤具有ELKS-RET重排（105例中的1例，1%）。总之，我们在台湾105例散发性PTC中的8例（8%）中检测到RET重排，这一发生率远低于此前报道的该人群发生率，但与其他国家使用类似方法报道的发生率相当。RET嵌合癌基因仅占台湾PTC的一小部分。
