Department of Surgery, Jersey Shore University Medical Center, Neptune, NJ 07754, USA.
Surgery. 2010 Dec;148(6):1274-80; discussion 1280-1. doi: 10.1016/j.surg.2010.09.004.
Single nucleotide polymorphisms (SNPs) may function as modifiers of the RET proto-oncogene, resulting in the expression of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). We present 2 non-related Italian-American families (Family 1, n = 107; Family 2, n = 31) with the RET V804M mutation. We have correlated the presence of specific SNPs and the rare RET V804M mutation to MTC, C-cell hyperplasia (CCH), and PTC.
Sequencing was performed on exons 10, 11, and 13-16 of the RET proto-oncogene. The presence of MTC, CCH, and PTC were correlated to specific SNPs.
In both families, 3 SNPs in exon 11 (G691S), exon 13 (L769L), and exon 15 (S904S) were detected in 100% of patients with overt MTC. The SNP L769L was present in all patients including patients with PTC, MTC, and CCH.
SNP analysis revealed a similar pattern between the 2 families. SNPs in exon 11 (G691S) and exon 15 (S904S) appear to influence the development of MTC. A SNP in exon 13 (L769L) may serve as a modifier in the development of simultaneous MTC and PTC, as well as presentation of MTC, in patients with the RET V804M mutation.
单核苷酸多态性（SNP）可能作为 RET 原癌基因的修饰物，导致髓样甲状腺癌（MTC）和甲状腺乳头状癌（PTC）的表达。我们介绍了两个无血缘关系的意大利裔美国家庭（家族 1，n = 107；家族 2，n = 31），这些家庭都携带有 RET V804M 突变。我们已经将特定 SNP 的存在与罕见的 RET V804M 突变与 MTC、C 细胞增生（CCH）和 PTC 相关联。
对 RET 原癌基因的外显子 10、11 和 13-16 进行测序。将 MTC、CCH 和 PTC 的存在与特定 SNP 相关联。
在这两个家族中，在外显子 11（G691S）、外显子 13（L769L）和外显子 15（S904S）中发现了 3 个 SNP，在有明显 MTC 的患者中，这 3 个 SNP 的出现率为 100%。L769L SNP 存在于所有患者中，包括患有 PTC、MTC 和 CCH 的患者。
SNP 分析揭示了这两个家族之间的相似模式。外显子 11（G691S）和外显子 15（S904S）中的 SNP 似乎影响 MTC 的发展。外显子 13（L769L）中的 SNP 可能作为 RET V804M 突变患者中同时发生 MTC 和 PTC 以及 MTC 表现的修饰物。
