Kruse R, Rütten A, Lamberti C, Hosseiny-Malayeri H R, Wang Y, Ruelfs C, Jungck M, Mathiak M, Ruzicka T, Hartschuh W, Bisceglia M, Friedl W, Propping P
Institute of Human Genetics, Friedrich-Wilhelms University, Bonn, Germany.
Am J Hum Genet. 1998 Jul;63(1):63-70. doi: 10.1086/301926.
Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the coincidence of at least one sebaceous skin tumor and one internal malignancy. About half of MTS patients are affected by colorectal cancer. In a subgroup of MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC). The purpose of this study was to examine to what extent germ-line mutations in DNA MMR genes are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients with sebaceous skin tumors and colorectal cancer, and we examined their skin and visceral tumors for microsatellite instability. All the patients exhibited high genomic instability in at least one tumor. The search for germ-line mutations in the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is the first systematic search for germ-line mutations in patients ascertained on the basis of sebaceous skin tumors. Our results indicate that (1) MTS patients exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene; and (2) the subpopulation of MTS patients who are also affected by colorectal cancer, irrespective of family history and age at onset of tumors, may have a likelihood for an underlying DNA MMR defect similar to that for patients with a family history fulfilling the strict clinical criteria for HNPCC.
穆尔-托雷综合征（MTS）是一种常染色体显性疾病，其定义为至少一种皮脂腺皮肤肿瘤与一种内脏恶性肿瘤同时存在。约一半的MTS患者会患结直肠癌。在MTS患者的一个亚组中，该疾病存在潜在的DNA错配修复（MMR）缺陷，因此与遗传性非息肉病性结直肠癌（HNPCC）等位。本研究的目的是检查DNA MMR基因中的种系突变在多大程度上是MTS表型的潜在病因。我们确定了16例患有皮脂腺皮肤肿瘤和结直肠癌的MTS患者，并检测了他们皮肤和内脏肿瘤的微卫星不稳定性。所有患者至少在一种肿瘤中表现出高度的基因组不稳定性。在13例MTS患者中寻找hMSH2和hMLH1基因的种系突变，发现9例（69%）有截短突变：hMSH2基因有8个突变，hMLH1基因有1个突变。这是首次对基于皮脂腺皮肤肿瘤确诊的患者进行种系突变的系统研究。我们的结果表明：（1）MTS患者中hMSH2基因的突变明显多于hMLH1基因；（2）无论家族史和肿瘤发病年龄如何，同时患有结直肠癌的MTS患者亚组，其潜在DNA MMR缺陷的可能性可能与符合HNPCC严格临床标准家族史的患者相似。
