Here, we present a rare case of a patient who developed multiple primary melanomas within the boundaries of two nevi depigmentosa. The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole-exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline MC1R V92M and TYR R402Q polymorphisms and a MET E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient-reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun-damaged skin, the patient's melanomas harbored somatic mutations in CDKN2A (splice site), NF1, and ATRX and had a tumor mutation burden in the 90–95th percentile for melanoma.

中文翻译：

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先天性色素痣边界内多发原发性黑色素瘤的遗传分析

在这里，我们介绍了一个罕见的病例，该病例在两个色素脱除痣的边界内发生了多个原发性黑色素瘤。切除黑色素瘤，作为预防措施，去除色素痣的剩余部分。我们对脱色素痣、邻近正常皮肤和唾液的切除组织进行了全外显子组测序，以解释这一有趣的现象。我们还对其中一种黑色素瘤组织进行了 GeneTrails 综合实体瘤面板分析。遗传分析揭示了种系MC1R V92M 和TYR R402Q 多态性和METE168D 种系突变可能增加了黑色素瘤发展的风险。这种遗传易感性，加上患者报告的大量日晒和晒伤病史，由于缺乏光保护性黑色素，在脱色痣边界内更为严重，导致脱色痣黑色素细胞发生大量体细胞突变。符合这种慢性日晒损伤皮肤黑色素瘤发展的范例，患者的黑色素瘤在CDKN2A（剪接位点）、NF1和ATRX中具有体细胞突变，并且在黑色素瘤的 90-95% 之间具有肿瘤突变负担。