Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Pigment Cell Melanoma Res. 2022 Mar;35(2):229-237. doi: 10.1111/pcmr.13017. Epub 2021 Oct 27.
Tumor heterogeneity is a relevant hallmark of melanoma due to the high mutation burden and immunogenicity commonly encountered. Heterogeneity at the histologic level frequently corresponds to heterogeneity at the molecular level. A better understanding of this feature of malignancy can help refine the development of predictive biomarkers and to define more effective targeted therapies. Here, we describe a case of melanoma displaying a dual phenotype: a DPN-like/plexiform portion in conjunction with a conventional epithelioid morphology. Molecular studies revealed shared BRAF and PTEN mutations in both components but a CTNNB1 mutation was exclusively found in the DPN-like area of the tumor, consistent with the distinct morphology observed. There was considerable heterogeneity in sequence variants identified in the two regions. Gene expression analysis highlighted differentially regulated genes between the two histologies, including a relevant cluster of genes in the receptor tyrosine kinase (RTK) family and related signaling pathways upregulated in the DPN-like/plexiform area.
肿瘤异质性是黑色素瘤的一个重要特征，这是由于常见的高突变负担和免疫原性。组织学水平的异质性经常对应于分子水平的异质性。更好地了解这种恶性特征有助于完善预测生物标志物的开发，并定义更有效的靶向治疗方法。在这里，我们描述了一个黑色素瘤病例，其表现出双重表型：DNP 样/丛状部分与常规上皮样形态相结合。分子研究显示两个成分中均存在 BRAF 和 PTEN 突变共享，但 CTNNB1 突变仅在肿瘤的 DNP 样区域发现，与观察到的不同形态一致。在两个区域鉴定的序列变异存在相当大的异质性。基因表达分析突出了两种组织学之间差异调控的基因，包括受体酪氨酸激酶 (RTK) 家族中的一个相关基因簇及其在 DNP 样/丛状区域上调的相关信号通路。
