Chan T L, Yuen S T, Chung L P, Ho J W, Kwan K, Fan Y W, Chan A S, Leung S Y
Department of Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong.
Genes Chromosomes Cancer. 1999 Jun;25(2):75-81.
Turcot's syndrome is characterized clinically by the occurrence of primary brain tumor and colorectal tumor and has in previous reports been shown to be associated with germline mutations in the genes APC, hMLH1, and hPMS2. Here we describe three patients with Turcot's syndrome, each having colorectal adenocarcinoma and malignant glioma. All the colorectal and brain tumors from these patients showed replication errors in most of the microsatellite loci investigated. Search for underlying germline mutations in the nucleotide mismatch repair genes revealed three different hMSH2 mutations. All colorectal tumors showed a frameshift in the A(10) tract in the coding sequence of the transforming growth factor beta type II receptor (TGFBRII) gene, but no such change was detected in any of the brain tumors. Frameshift mutation in the BAX gene was found in one colon carcinoma and mutations in insulin-like growth factor type II receptor (IGFIIR) gene in one glioma. Our data have broadened the possible mutation spectrum of patients with Turcot's syndrome. The difference in the mutation spectrum of TGFBRII, BAX, and IGFIIR between brain and colorectal tumors in these individuals suggests that the mutator phenotype may target different pathogenic pathways in the oncogenic process of the two organs.
Turcot综合征在临床上的特征是原发性脑肿瘤和结直肠肿瘤的发生，先前的报告显示其与APC、hMLH1和hPMS2基因的种系突变有关。在此，我们描述了三名Turcot综合征患者，他们均患有结直肠腺癌和恶性胶质瘤。这些患者的所有结直肠肿瘤和脑肿瘤在大多数检测的微卫星位点均显示复制错误。对核苷酸错配修复基因潜在种系突变的搜索发现了三种不同的hMSH2突变。所有结直肠肿瘤在转化生长因子βⅡ型受体（TGFBRII）基因编码序列的A(10)区域均显示移码，但在任何脑肿瘤中均未检测到此类变化。在一例结肠癌中发现了BAX基因的移码突变，在一例胶质瘤中发现了胰岛素样生长因子Ⅱ型受体（IGFIIR）基因的突变。我们的数据拓宽了Turcot综合征患者可能的突变谱。这些个体脑肿瘤和结直肠肿瘤之间TGFBRII、BAX和IGFIIR突变谱的差异表明，错配修复缺陷表型可能在这两个器官的致癌过程中靶向不同的致病途径。
