The WHO classification identifies nine classes of melanocytic proliferations according to location, UV exposure, histological, and genetic features. Only a minority of lesions remain unclassified. We describe five cases that harbored either an ERBIN-RASGRF2 or an ATP2B4-RASGRF2 in-frame fusion transcript. These lesions were collected from different studies, unified only by the lack of identifiable known mutations, with a highly variable phenotype. One case was a large abdominal congenital nevus, three were slowly growing pigmented nodules, and the last was an ulcerated nodule arising on the site of a preexisting small nevus, known since childhood. The latter was diagnosed as a 4 mm thick melanoma with loss of BAP1 expression. The four other cases were compound, melanocytic proliferations with an unusual deep pattern of small dense nests of bland melanocytes encased in a fibrous background. The RASGRF2 fusion was confirmed by a break-apart FISH technique. Array CGH performed in three cases found non-recurrent secondary copy number alterations. Follow-up was uneventful. In silico analysis identified a single RASGRF2 fusion in the TCGA pan-cancer database, whereas RASGRF2 variants were stochastically distributed in all cancer subtypes.

中文翻译：

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RASGRF2 基因融合在具有不同形态特征的各种黑素细胞病变中鉴定

WHO 分类根据位置、紫外线照射、组织学和遗传特征确定了九类黑色素细胞增殖。只有少数病变仍未分类。我们描述了五个携带 ERBIN-RASGRF2或ATP2B4-RASGRF2的病例帧内融合转录本。这些病变是从不同的研究中收集的，仅通过缺乏可识别的已知突变来统一，具有高度可变的表型。一个病例是一个大的腹部先天性痣，三个是缓慢生长的色素结节，最后一个是一个溃疡结节，出现在从小就知道的小痣的部位。后者被诊断为 4 mm 厚的黑色素瘤，BAP1 表达缺失。其他四个病例是复合的黑素细胞增殖，具有不寻常的深层模式，即包裹在纤维背景中的小而密集的温和黑素细胞巢。RASGRF2 _融合通过分离 FISH 技术得到证实。在三个案例中进行的阵列 CGH 发现非复发性次要拷贝数改变。后续进展顺利。计算机分析确定了TCGA 泛癌数据库中的单个RASGRF2融合，而RASGRF2变体随机分布在所有癌症亚型中。