Molecular characterization of biphenotypic epithelioid and plexiform melanoma with deep penetrating nevus‐like features. (27th October 2021)

• Record Type: Journal Article
• Authors: Giubellino, Alessio; Nelson, Andrew C.; He, Yuyu; Munro, Sarah A.; Song, Kyu Young; Glitza Oliva, Isabella C.; Torres‐Cabala, Carlos
• Is Part Of: Pigment cell & melanoma research. Volume 35:Number 2(2022)
• Page Start: 229
• Page End: 237
• Publication Date: 2021-10-27
• Subjects: deep penetrating nevus -- epithelial‐mesenchimal transition -- heterogeneity -- melanoma -- receptor tyrosine kinases; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.13017
• Languages: English
• ISSNs: 1755-1471

Abstract

Abstract: 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.