Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gαq/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gαs pathway. We hypothesize that PRKC fusions have greater genomic overlap with blue nevi compared with PRKAR1A-inactivated PEMs. We characterized the clinical and morphologic features of 21 PRKC and PRKACB fusion melanocytic tumors and compared this to PRKAR1A mutated PEMs. To test our hypothesis regarding greater genomic overlap between PRKC fusions and blue nevi relative to PRKAR1A mutated PEMs, we performed a principal component analysis (PCA) using mRNA expression data. Lastly, we performed a meta-analysis focusing on the outcome data of PRKC fusions. PRKC fusions occur at a younger median age than PRKAR1A mutated PEMs (16 vs. 27). Histologically, PRKC fusions have solid aggregates of epithelioid melanocytes not typical of PRKAR1A mutated PEMs. The PCA plot showed no overlap between the PRKC fusion group and the PRKAR1A-mutated PEMs. There was a significant overlap between PRKC fusions and blue nevi. A meta-analysis of PRKC fusion cases in the literature suggests melanoma is uncommon, but the loss of BAP-1 nuclear expression may be associated with an adverse prognosis as in tumors from the blue nevus family. PRKC fusion melanocytic tumors have greater genomic overlap with blue nevi compared with PRKAR1A mutated PEMs. We recommend categorizing benign PRKC fusion melanocytic tumors as blue fusion nevi/tumors.

中文翻译：

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PRKC 融合黑色素细胞瘤，黑色素细胞肿瘤的一个亚组，与蓝痣更接近于与PRKAR1A灭活的色素上皮样黑素细胞瘤的对齐。


形态学分类为色素上皮样黑素细胞瘤 （PEM） 的肿瘤在基因组上是多种多样的，其中 2 种最常见的基因组亚型是 PRKC 融合或 PRKAR1A 灭活突变。PRKC 融合激活类似于蓝痣的 Gαq/11 通路。相反，PRKAR1A 中的失活突变会激活 Gαs 通路。我们假设与 PRKAR1A 灭活的 PEM 相比，PRKC 融合与蓝痣的基因组重叠更大。我们表征了 21 例 PRKC 和 PRKACB 融合黑色素细胞肿瘤的临床和形态学特征，并将其与 PRKAR1A 突变的 PEM 进行了比较。为了检验我们关于 PRKC 融合和蓝痣相对于 PRKAR1A 突变 PEM 之间基因组重叠更大的假设，我们使用 mRNA 表达数据进行了主成分分析 （PCA）。最后，我们进行了一项荟萃分析，重点关注 PRKC 融合的结局数据。PRKC 融合的中位年龄比 PRKAR1A 突变的 PEM 更年轻 （16 vs. 27）。在组织学上，PRKC 融合具有上皮样黑素细胞的固体聚集体，这与 PRKAR1A 突变的 PEM 不同。PCA 图显示 PRKC 融合组和 PRKAR1A 突变的 PEMs 之间没有重叠。PRKC 融合和蓝痣之间存在显着重叠。文献中对 PRKC 融合病例的荟萃分析表明，黑色素瘤并不常见，但 BAP-1 核表达的缺失可能与不良预后有关，就像蓝痣家族的肿瘤一样。与突变的 PEM 相比，PRKC 融合黑色素细胞肿瘤与蓝痣PRKAR1A基因组重叠更大。我们建议将良性 PRKC 融合黑色素细胞肿瘤分类为蓝色融合痣/肿瘤。