Peaston A E, Camacho M L, Norris M D, Haber M, Marsh D J, Robinson B G, Hyland V J, Marshall G M
Children's Cancer Institute Australia, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Mol Cell Probes. 1998 Aug;12(4):239-42. doi: 10.1006/mcpr.1998.0181.
Specific germline mutations in the RET proto-oncogene predispose to the familial cancer syndromes: multiple endocrine neoplasia (MEN) types 2A and 2B, and familial medullary thyroid carcinoma. Expression of the RET receptor tyrosine kinase is tightly restricted to tumours of neural crest origin, such as neuroblastoma, and neuroblastoma has been observed in RET transgenic mice. Neuroblastoma tumour cell lines transfected with the MEN2A RET gene exhibit spontaneous neuritic differentiation, whereas MEN2B-type RET transfectants demonstrate altered cell adhesion and enhanced metastatic potential. In this study, the authors examined genomic DNA from 26 primary neuroblastoma tumours for MEN2A and MEN2B RET mutations, using restriction enzyme digestion of polymerase chain reaction products as an alternative to direct sequencing. Examination of RET exons 10 (codons 611, 618, 620), 11 (codons 632, 633, 634) and 16 (codon 918) in all 26 tumours revealed no RET mutations. Taken together these data suggest that abnormalities of the RET signalling pathway, rather than oncogenic, MEN2-type RET activation by mutation, may play a role in neuroblastoma tumorigenesis.
RET原癌基因中的特定种系突变易导致家族性癌症综合征：2A和2B型多发性内分泌腺瘤病（MEN）以及家族性甲状腺髓样癌。RET受体酪氨酸激酶的表达严格限于神经嵴起源的肿瘤，如神经母细胞瘤，并且在RET转基因小鼠中已观察到神经母细胞瘤。用MEN2A RET基因转染的神经母细胞瘤肿瘤细胞系表现出自发性神经突分化，而MEN2B型RET转染子表现出细胞黏附改变和转移潜能增强。在本研究中，作者使用聚合酶链反应产物的限制性酶切消化替代直接测序，检测了26例原发性神经母细胞瘤肿瘤的基因组DNA中的MEN2A和MEN2B RET突变。对所有26个肿瘤中的RET外显子10（密码子611、618、620）、11（密码子632、633、634）和16（密码子918）进行检测，未发现RET突变。这些数据综合起来表明，RET信号通路的异常而非致癌性的、由突变激活的MEN2型RET，可能在神经母细胞瘤的肿瘤发生中起作用。
