Genomic and signalling pathway characterization of the NZM panel of melanoma cell lines: A valuable model for studying the impact of genetic diversity in melanoma

Pigment Cell Melanoma Res. 2021 Jan;34(1):136-143. doi: 10.1111/pcmr.12908. Epub 2020 Jul 4.

Abstract

Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), including using whole-exome and RNA sequencing to analyse genetic variants and gene expression changes in a subset of this panel. Lines possessing all major melanoma genotypes were identified, and hierarchical clustering of gene expression profiles revealed four broad subgroups of cell lines. Immunogenotyping identified a range of HLA haplotypes as well as expression of neoantigens and cancer-testis antigens in the lines. Together, these characteristics make the NZM panel a valuable resource for cell-based, immunological and xenograft studies to better understand the diversity of melanoma biology and the responses of melanoma to therapeutic interventions.

Keywords: BRAF; CTTNB1; KRAS; NF1; NRAS; PDGFRA; PIK3CA; cancer; immunotherapy; melanoma; molecular subtypes; neoantigen; testis antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Exome Sequencing
  • Exome*
  • Gene Expression Regulation, Neoplastic*
  • Genomics / methods*
  • Humans
  • Melanoma / genetics*
  • Melanoma / secondary
  • Models, Biological*
  • Mutation*
  • Signal Transduction
  • Transcriptome
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor