Klugbauer S, Lengfelder E, Demidchik E P, Rabes H M
Institute of Pathology, Ludwig Maximillyians University of Munich, Germany.
Oncogene. 1995 Dec 21;11(12):2459-67.
RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using primers suited to amplify fragments in different quantities depending on the presence or absence of RET rearrangements in the tissues. The type of rearrangement was determined by RT-PCR and direct sequencing using primers for ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3 than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors had lymph node metastasis while half of the tumors with wild-type cRET had not. More than half of the cases with ret/PTC3 expressed not only the ELE/RET transcript as expected, but also the RET/ELE transcript. Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.
在切尔诺贝利事故后白俄罗斯受放射性沉降物影响的儿童甲状腺乳头状癌(PTC)中研究了RET重排情况。为了检测甲状腺切除标本小组织样本中的RET重排(12例儿童PTC;2例成人PTC和1例成人滤泡癌;4例儿童和4例成人的非肿瘤性甲状腺组织作为对照),开发了一种逆转录多重PCR,使用适合根据组织中RET重排的有无来扩增不同数量片段的引物。通过逆转录PCR和使用针对ret/PTC1、2和3的引物进行直接测序来确定重排类型。儿童甲状腺乳头状癌中有三分之二显示RET重排,ret/PTC3的频率比ret/PTC1高3倍。未检测到ret/PTC2。所有RET重排阳性肿瘤均有淋巴结转移,而野生型cRET肿瘤中有一半没有。超过一半的ret/PTC3病例不仅如预期表达ELE/RET转录本,还表达RET/ELE转录本。10号染色体上涉及RET和相邻H4或ELE基因的染色体内重排在白俄罗斯切尔诺贝利污染区儿童甲状腺癌中是非常常见的事件。