BRAF Wild-Type Melanoma in Situ Arising In a BRAF V600E Mutant Dysplastic Nevus
BRAF Wild-Type Melanoma in Situ Arising In a BRAF V600E Mutant Dysplastic Nevus
复制标题
DOI：
10.1001/jamadermatol.2014.3775
复制
发表时间：
2015-04-01
期刊：
影响因子：
10.9
通讯作者：
Soyer, H. Peter
中科院分区：
文献类型：
--
作者：
Tan, Jean-Marie;Lin, Lynlee L.;Soyer, H. Peter
重要性 BRAF V600E 突变占皮肤黑色素瘤中发现的大部分 BRAF 突变，并且也常见于痣中。我们使用皮肤镜靶向取样和微活检装置与 DNA 序列分析相结合，以突出多组分黑素细胞增殖中的 BRAF V600E 异质性。该采样技术展示了在临床环境中体内应用的前景。 观察 一名 50 多岁的菲茨帕特里克 II 型皮肤男性，背部出现不规则色素黑素细胞病变，符合黑色素瘤特异性皮肤镜标准，并对病变进行了诊断性剃须切除。组织病理学分析显示，发育不良痣中存在原位黑色素瘤。在病变处采集皮肤镜靶向微活检标本，并对提取的 DNA 样本进行 BRAF 和 NRAS 突变的基因分型。原位黑色素瘤仅显示 BRAF 野生型结果，而发育不良痣则显示 BRAF 野生型和 BRAF V600E 突变。所有 DNA 样本的测序均显示 NRAS 野生型基因型。 结论和相关性 对发育不良痣中产生的黑色素瘤进行皮肤镜靶向取样和基因分型揭示了表型-基因型悖论，该悖论混淆了 BRAF 和 NRAS 突变在黑色素瘤发病机制中的独特意义。需要进一步的研究来调查与黑色素瘤发生相关的其他候选基因的重要性。
IMPORTANCE The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting.OBSERVATIONS A man in his 50s with Fitzpatrick skin type II presented with an irregularly pigmented melanocytic lesion on his back that met melanoma-specific dermoscopic criteria, and diagnostic shave excision of the lesion was performed. Histopathologic analysis revealed a melanoma in situ arising in a dysplastic nevus. Dermoscopy-targeted microbiopsy specimens were taken across the lesion, and genotyping was carried out on extracted DNA samples for BRAF and NRAS mutations. The melanoma in situ showed only BRAF wild-type results, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype.CONCLUSIONS AND RELEVANCE Dermoscopy-targeted sampling and genotyping of a melanoma in situ arising in a dysplastic nevus revealed a phenotype-genotype paradox that confounds the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis. Further studies are required to investigate the importance of other candidate genes linked to melanomagenesis.