4.5 Article

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

Journal

PIGMENT CELL & MELANOMA RESEARCH
Volume 34, Issue 1, Pages 136-143

Publisher

WILEY
DOI: 10.1111/pcmr.12908

Keywords

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

Funding

  1. Auckland and Northland Branch of the Cancer Society of New Zealand
  2. Health Research Council of New Zealand
  3. Maurice Wilkins Centre for Molecular Biodiscovery

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The study characterizes a panel of cell lines from metastatic melanomas, identifying four subgroups of cell lines based on gene expression profiles and detecting HLA haplotypes and neoantigens in the lines through immunogenotyping. The NZM panel serves as a valuable resource for understanding the diversity of melanoma biology and the responses of melanoma to therapeutic interventions.
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.

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