Marsh D J, Andrew S D, Eng C, Learoyd D L, Capes A G, Pojer R, Richardson A L, Houghton C, Mulligan L M, Ponder B A, Robinson B G
Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, N.S.W., Australia.
Cancer Res. 1996 Mar 15;56(6):1241-3.
Inherited cancer syndromes predispose an individual to development of specific tumors. Somatic and germline mutations in the same tumor suppressor gene, as described in Knudson's two-mutation model, are well recognized. Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have not been identified in tumors from individuals with MEN 2, although they have been well documented in sporadic MEN 2-related tumors. We have identified, among 16 MEN 2 cases with well-defined RET germline mutations, a somatic missense mutation at codon 918 of RET in 3 of 15 MTCs and in a sample with hyperplastic C-cells (presumed precursor to hereditary MTC). We suggest that the presence of a somatic mutation, in addition to the preexisting germline mutation in hereditary MTCs, may contribute to tumorigenesis in vivo.
遗传性癌症综合征使个体易患特定肿瘤。如克努森的双突变模型所述，同一肿瘤抑制基因中的体细胞突变和种系突变已得到充分认识。编码受体酪氨酸激酶的RET原癌基因中的遗传性突变使个体易患2型多发性内分泌肿瘤（MEN 2）癌症综合征。这些综合征的主要组成肿瘤是甲状腺髓样癌（MTC）。迄今为止，在MEN 2患者的肿瘤中尚未发现RET的体细胞突变，尽管它们在散发性MEN 2相关肿瘤中已有充分记录。我们在16例具有明确RET种系突变的MEN 2病例中，在15例MTC中的3例以及1例增生性C细胞（推测为遗传性MTC的前体）样本中，发现了RET第918密码子的体细胞错义突变。我们认为，除了遗传性MTC中预先存在的种系突变外，体细胞突变的存在可能在体内促进肿瘤发生。
