Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Dermatol. 2021 Aug;48(8):1268-1272. doi: 10.1111/1346-8138.15919. Epub 2021 Apr 27.
A sebaceous nevus is a congenital skin hamartoma caused by postzygotic HRAS or KRAS mosaic mutations. With age, affected individuals may develop secondary tumors within a sebaceous nevus. RAS mutations are harbored from the onset of sebaceous nevus, and further mutations can be expected to be required in order to explain the initiation of secondary tumors. However, genetic analyses of the secondary tumors have not been conducted. Herein, we describe the rare coexistence of a poroma and a trichoblastoma arising in a sebaceous nevus. This is the first report of an investigation of multiple genes in a secondary tumor in an SN. First, HRAS c.37G>C, which is the common mutation in sebaceous nevus, was detected in all three lesions (sebaceous nevus, poroma, and trichoblastoma). Next, to elucidate the potential second-hit mutations in the secondary poroma and trichoblastoma, we applied a panel sequencing for skin cancers that was newly developed in our institution. Our comparison of the mutational profile of 95 skin cancer-related genes in each of the three lesions newly revealed TP53 p.R158P in the poroma and NOTCH2 p.G329S in the trichoblastoma. TP53 p.R158P has been determined as a pathogenic mutation in other tumors, and NOTCH2 p.G329S was a novel mutation. We identified two novel mutations that may have contributed to the pathogenesis of the secondary tumor's development. The roles of the mutations remain unclear.
皮脂腺痣是一种后天性皮肤错构瘤，由合子后 HRAS 或 KRAS 嵌合体突变引起。随着年龄的增长，受影响的个体可能会在皮脂腺痣内发展出继发性肿瘤。RAS 突变从皮脂腺痣发病时就存在，为了解释继发性肿瘤的发生，预计还需要进一步的突变。然而，尚未对继发性肿瘤进行遗传分析。在此，我们描述了一种罕见的皮脂腺痣中同时存在汗腺瘤和毛发上皮瘤的情况。这是首例对 SN 中继发性肿瘤进行多种基因研究的报道。首先，在所有三个病变（皮脂腺痣、汗腺瘤和毛发上皮瘤）中均检测到 HRAS c.37G>C，这是皮脂腺痣的常见突变。接下来，为了阐明继发性汗腺瘤和毛发上皮瘤的潜在二次打击突变，我们应用了我们机构新开发的皮肤癌 panel 测序。我们对三个病变中 95 个皮肤癌相关基因的突变谱进行了比较，在汗腺瘤中发现了 TP53 p.R158P，在毛发上皮瘤中发现了 NOTCH2 p.G329S。TP53 p.R158P 已被确定为其他肿瘤的致病性突变，而 NOTCH2 p.G329S 是一种新的突变。我们鉴定了两个可能导致继发性肿瘤发展的新突变。这些突变的作用仍不清楚。
