Kimura T, Yoshimoto K, Yokogoshi Y, Saito S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Endocr J. 1995 Aug;42(4):517-25. doi: 10.1507/endocrj.42.517.
Medullary thyroid carcinoma (MTC) and pheochromocytoma appear in either a sporadic or a hereditary form as components of multiple endocrine neoplasia (MEN). Many germline mutations of the RET proto-oncogene have been reported in patients with MEN 2A and 2B, and familial MTC (FMTC). To elucidate the etiological roles in tumorigenesis of sporadic MTCs and pheochromocytomas, mutations in the cysteine-rich region of the RET proto-oncogene were analyzed by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Exons 10 and 11 were studied in genomic DNAs from 3 clinically apparent sporadic MTCs, MTCs and pheochromocytomas from 2 patients with MEN 2A, 1 with FMTC, 4 with MEN 2B, 3 with neurofibromatosis type 1 (NF1), 12 sporadic pheochromocytomas and an MTC cell line, TT. All tumors from two patients with MEN 2A and one patient with FMTC had mutations at codon 618 and 634 as well as their leukocytes, reflecting their germline mutations. In this region, no mutations were detected in any tumors from patients with MEN 2B and NF1, and sporadic pheochromocytomas. But mutations were detected and identified in 3 clinically apparent sporadic MTCs and TT cells. A 6 base pair (bp) deletion causing the loss of a cysteine residue at codon 634 and a mutation causing substitution from cysteine to tyrosine at codon 634 were detected in 2 sporadic MTCs as somatic events. In a female patient diagnosed as having sporadic MTC, a mutation at codon 618 was detected not only in tumor tissues, but also in her leukocytes, suggesting a germline mutation of the RET proto-oncogene.(ABSTRACT TRUNCATED AT 250 WORDS)
甲状腺髓样癌（MTC）和嗜铬细胞瘤以散发性或遗传性形式出现，作为多发性内分泌腺瘤病（MEN）的组成部分。在MEN 2A和2B以及家族性MTC（FMTC）患者中，已报道了RET原癌基因的许多种系突变。为了阐明散发性MTC和嗜铬细胞瘤在肿瘤发生中的病因学作用，通过聚合酶链反应-单链构象多态性（PCR-SSCP）分析，对RET原癌基因富含半胱氨酸区域的突变进行了分析。研究了来自3例临床显性散发性MTC、2例MEN 2A患者的MTC和嗜铬细胞瘤、1例FMTC患者、4例MEN 2B患者、3例1型神经纤维瘤病（NF1）患者、12例散发性嗜铬细胞瘤的基因组DNA中的第10和11外显子，以及1个MTC细胞系TT。2例MEN 2A患者和1例FMTC患者的所有肿瘤及其白细胞在密码子618和634处均有突变，反映了它们的种系突变。在该区域，MEN 2B患者、NF1患者和散发性嗜铬细胞瘤的任何肿瘤中均未检测到突变。但在3例临床显性散发性MTC和TT细胞中检测到并鉴定出了突变。在2例散发性MTC中检测到一个6碱基对（bp）缺失导致密码子634处半胱氨酸残基丢失，以及一个密码子634处半胱氨酸被酪氨酸替代的突变，这些均为体细胞事件。在一名被诊断为散发性MTC的女性患者中，不仅在肿瘤组织中检测到密码子618处的突变，在其白细胞中也检测到该突变，提示RET原癌基因的种系突变。（摘要截取自250字）
