Simic Dario, Dummer Reinhard, Freiberger Sandra N, Ramelyte Egle, Barysch Marjam-Jeanette
Department of Dermatology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006 Zurich, Switzerland.
Genes (Basel). 2021 May 20;12(5):781. doi: 10.3390/genes12050781.
We investigated the mutational landscape of skin tumors in patients with Muir-Torre Syndrome (MTS) a hereditary autosomal dominant mismatch repair disorder of increased cancer susceptibility, and examined mutations other than in the DNA mismatch repair (MMR) genes.
This retrospective single-center case series included seven patients with the diagnosis of Muir-Torre Syndrome with precise medical history and family history. Mutational analysis of tumor samples Formalin-fixed paraffin-embedded tissue blocks of skin lesions associated with Muir-Torre Syndrome were used for further analysis. All skin tumors were analyzed with the Oncomine Comprehensive Assay v3 (Life Technologies), which includes 161 of the most relevant cancer driver genes.
Eleven skin neoplasms (nine sebaceous tumors, one melanoma, one cutaneous squamous cell carcinoma) were diagnosed in seven patients. In two patients, visceral malignancies preceded the diagnosis of the skin tumors and one patient was diagnosed with a visceral malignancy after a sebaceous tumor. History of familial cancer of Lynch Syndrome (LS) was reported in three patients. The most frequently detected mutation was in the gene, followed by mutations in the and gene. Conclusion, this study provides a molecular analysis of Muir-Torre Syndrome associated and non-associated skin tumors in patients with Muir-Torre Syndrome. Patients with sebaceous lesions should undergo microsatellite instability analysis and accurate evaluation of personal and family history to detect a possible Muir-Torre syndrome. As secondary malignancies may appear years after the first occurrence of sebaceous tumors, lifelong screening is mandatory.
我们研究了穆尔-托雷综合征（MTS）患者皮肤肿瘤的突变图谱，MTS是一种遗传性常染色体显性错配修复疾病，癌症易感性增加，并检查了DNA错配修复（MMR）基因以外的突变。
这项回顾性单中心病例系列研究纳入了7例诊断为穆尔-托雷综合征的患者，他们有精确的病史和家族史。肿瘤样本的突变分析 与穆尔-托雷综合征相关的皮肤病变的福尔马林固定石蜡包埋组织块用于进一步分析。所有皮肤肿瘤均采用Oncomine Comprehensive Assay v3（Life Technologies）进行分析，该检测包括161个最相关的癌症驱动基因。
7例患者共诊断出11例皮肤肿瘤（9例皮脂腺肿瘤、1例黑色素瘤、1例皮肤鳞状细胞癌）。2例患者在皮肤肿瘤诊断之前就已出现内脏恶性肿瘤，1例患者在诊断出皮脂腺肿瘤后被诊断出内脏恶性肿瘤。3例患者报告有林奇综合征（LS）家族癌症病史。最常检测到的突变位于 基因，其次是 基因和 基因的突变。结论，本研究对穆尔-托雷综合征患者相关和不相关的皮肤肿瘤进行了分子分析。有皮脂腺病变的患者应进行微卫星不稳定性分析，并准确评估个人和家族病史，以检测可能的穆尔-托雷综合征。由于继发性恶性肿瘤可能在首次出现皮脂腺肿瘤数年之后出现，因此终身筛查是必要的。
