Congenital melanocytic nevus (CMN) represent a benign proliferative skin disease in the epidermis and dermis. CMN are historically known to be associated with activating NRAS or BRAF mutations. Melanoma frequently harbors the BRAF p.Val600Glu mutation, which is also commonly found in benign nevi. A recent study reported mutation of MAP2K1, a downstream effector of the RAS-RAF-MEK pathway, in melanoma with an overall frequency of 8%. Later, in 2019, Jansen P detected one activating MAP2K1 mutation in acral nevi. However, it is unknown whether MAP2K1 mutations are common in CMN, and how MAP2K1 contributes to the pathogenesis of CMN remains to be determined. In this study, we report one patient clinically and histologically diagnosed with CMN, with the MAP2K1 germline mutation and a BRAF p.Val600Glu somatic hit in the lesion. To the best of our knowledge, this is the first report of the coexistence of mutated BRAF and MAP2K1 in CMN, which may suggest that MAP2K1 mutations contribute to the occurrence and development of nevus expanding our knowledge of the genetics of CMN.

中文翻译：

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先天性黑素细胞痣的新基因改变：MAP2K1 胚系突变与 BRAF 体细胞突变

先天性黑素细胞痣（CMN）代表表皮和真皮中的良性增生性皮肤病。历史上已知 CMN 与激活 NRAS 或 BRAF 突变有关。黑色素瘤经常携带 BRAF p.Val600Glu 突变，这在良性痣中也很常见。最近的一项研究报告了 MAP2K1（RAS-RAF-MEK 通路的下游效应器）在黑色素瘤中的突变，总频率为 8%。后来，在 2019 年，Jansen P 在肢端痣中检测到一个激活的 MAP2K1 突变。然而，尚不清楚 MAP2K1 突变在 CMN 中是否常见，MAP2K1 如何参与 CMN 的发病机制仍有待确定。在这项研究中，我们报告了一名临床和组织学诊断为 CMN 的患者，该患者具有 MAP2K1 种系突变和病变中的 BRAF p.Val600Glu 体细胞命中。