Multi-modal molecular programs regulate melanoma cell state

Miles C. Andrews, Junna Oba, Chang Jiun Wu, Haifeng Zhu, Tatiana Karpinets, Caitlin A. Creasy, Marie Andrée Forget, Xiaoxing Yu, Xingzhi Song, Xizeng Mao, A. Gordon Robertson, Gabriele Romano, Peng Li, Elizabeth M. Burton, Yiling Lu, Robert Szczepaniak Sloane, Khalida M. Wani, Kunal Rai, Alexander J. Lazar, Lauren E. HayduMatias A. Bustos, Jianjun Shen, Yueping Chen, Margaret B. Morgan, Jennifer A. Wargo, Lawrence N. Kwong, Cara L. Haymaker, Elizabeth A. Grimm, Patrick Hwu, Dave S.B. Hoon, Jianhua Zhang, Jeffrey E. Gershenwald, Michael A. Davies, P. Andrew Futreal, Chantale Bernatchez, Scott E. Woodman

Research output: Contribution to journalArticlepeer-review

Abstract

Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field.

Original languageEnglish
Article number4000
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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