Molecular profiling of Spitz nevi identified by digital RNA counting

Lisa M. Hillen, Milan S. Geybels, Dorit Rennspiess, Ivelina Spassova, Cathrin Ritter, Juergen C. Becker, Marjan Garmyn, Axel zur Hausen, Joost Van den Oord, Veronique Winnepenninckx*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

The molecular properties of benign melanocytic lesions are poorly understood. Only a few studies have been carried out on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expressions of 25 SN and 15 NCN were analyzed. Molecular profiling was performed using the RNA NanoString nCounter Gene Expression Platform (number of genes=770). Marker discovery was performed with a training set consisting of seven SN and seven NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and eight NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes were validated in the validation set (false discovery rate q≤0.13). In addition, using random forest and least absolute shrinkage and selection operator feature selection, a molecular signature of SN versus NCN was identified including 15 top-ranked genes. The present study identified a distinct molecular expression profile in SN compared with NCN, even when lesions were obtained from the same patients. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory, and extracellular matrix interactions as well as angiogenesis-associated processes in SN. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.

Original languageEnglish
Pages (from-to)510-520
Number of pages11
JournalMelanoma Research
Volume28
Issue number6
DOIs
Publication statusPublished - Dec 2018

Keywords

  • gene pathways
  • molecular signature
  • mRNA
  • nevocellular nevi
  • Spitz nevus
  • MALIGNANT-MELANOMA
  • GENE-EXPRESSION
  • NODE BIOPSY
  • GROWTH
  • CANCER
  • RESISTANCE
  • PATHOLOGY
  • SYSTEM
  • TUMORS

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