Mutation analysis of multiple pilomatricomas in a patient with myotonic dystrophy type 1 suggests a DM1-associated hypermutation phenotype

Molecular analysis of four pilomatricomas and one pilomatrical carcinoma in a patient with myotonic dystrophy type 1 demonstrate that the patient displayed hypermutability within his hair matrix cells targeting the catenin-beta gene which suggests a tissue and gene restricted hypermutation phenotype associated with DM1. Hereby we could disregard the hypothesis first proposed in 2009 that the untranslated repetitive RNA of the expanded DMPK gene directly enhances expression of b-catenin resulting in pilomatricomas as well as in various cancers which rely on activation of the WNT/APC/beta-catenin pathway. More molecular research on DM1 cancer predisposition will have to be performed in order to identify the mechanisms responsible for putative hypermutability in DM1 patients. NGS-panel sequencing data of the pilomatrical carcinoma are provided.

针对1型肌强直性营养不良（myotonic dystrophy type 1, DM1）患者体内的4例毛母质瘤（pilomatricomas）与1例毛母质癌（pilomatrical carcinoma）开展的分子分析结果显示，该患者的毛母质细胞中存在针对β-连环蛋白基因（catenin-beta gene）的高突变性，提示存在与DM1相关的组织及基因限制性高突变表型。借此本研究可推翻2009年首次提出的假说：即扩增型DMPK基因的非翻译重复RNA可直接上调β-连环蛋白的表达，进而诱发毛母质瘤及多种依赖WNT/APC/β-连环蛋白通路激活的癌症。未来需开展更多针对DM1癌症易感性的分子研究，以明确DM1患者出现潜在高突变性的具体机制。本研究附带提供该毛母质癌的NGS-panel测序数据。