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. Haydu, Matias 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 and Scott E. Woodman ()
Additional contact information
Miles C. Andrews: Monash University
Junna Oba: The University of Texas MD Anderson Cancer Center
Chang-Jiun Wu: The University of Texas MD Anderson Cancer Center
Haifeng Zhu: The University of Texas MD Anderson Cancer Center
Tatiana Karpinets: The University of Texas MD Anderson Cancer Center
Caitlin A. Creasy: The University of Texas MD Anderson Cancer Center
Marie-Andrée Forget: The University of Texas MD Anderson Cancer Center
Xiaoxing Yu: Keio University School of Medicine
Xingzhi Song: The University of Texas MD Anderson Cancer Center
Xizeng Mao: The University of Texas MD Anderson Cancer Center
A. Gordon Robertson: Canada’s Michael Smith Genome Sciences Center, BC Cancer
Gabriele Romano: The University of Texas MD Anderson Cancer Center
Peng Li: The University of Texas MD Anderson Cancer Center
Elizabeth M. Burton: The University of Texas MD Anderson Cancer Center
Yiling Lu: The University of Texas MD Anderson Cancer Center
Robert Szczepaniak Sloane: The University of Texas MD Anderson Cancer Center
Khalida M. Wani: The University of Texas MD Anderson Cancer Center
Kunal Rai: The University of Texas MD Anderson Cancer Center
Alexander J. Lazar: The University of Texas MD Anderson Cancer Center
Lauren E. Haydu: The University of Texas MD Anderson Cancer Center
Matias A. Bustos: Providence Saint John’s Health Center
Jianjun Shen: The University of Texas MD Anderson Cancer Center
Yueping Chen: The University of Texas MD Anderson Cancer Center
Margaret B. Morgan: The University of Texas MD Anderson Cancer Center
Jennifer A. Wargo: The University of Texas MD Anderson Cancer Center
Lawrence N. Kwong: The University of Texas MD Anderson Cancer Center
Cara L. Haymaker: The University of Texas MD Anderson Cancer Center
Elizabeth A. Grimm: The University of Texas MD Anderson Cancer Center
Patrick Hwu: The University of Texas MD Anderson Cancer Center
Dave S. B. Hoon: Providence Saint John’s Health Center
Jianhua Zhang: The University of Texas MD Anderson Cancer Center
Jeffrey E. Gershenwald: The University of Texas MD Anderson Cancer Center
Michael A. Davies: The University of Texas MD Anderson Cancer Center
P. Andrew Futreal: The University of Texas MD Anderson Cancer Center
Chantale Bernatchez: The University of Texas MD Anderson Cancer Center
Scott E. Woodman: The University of Texas MD Anderson Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31510-1

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