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- Title
Multi-modal molecular programs regulate melanoma cell state.
- Authors
Andrews, Miles C.; Oba, Junna; Wu, Chang-Jiun; Zhu, Haifeng; Karpinets, Tatiana; Creasy, Caitlin A.; Forget, Marie-Andrée; Yu, Xiaoxing; Song, Xingzhi; Mao, Xizeng; Robertson, A. Gordon; Romano, Gabriele; Li, Peng; Burton, Elizabeth M.; Lu, Yiling; Sloane, Robert Szczepaniak; Wani, Khalida M.; Rai, Kunal; Lazar, Alexander J.; Haydu, Lauren E.
- 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. The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features.
- Subjects
EPIGENOMICS; LINCRNA; NON-coding DNA; MELANOMA; PROTEIN microarrays; RNA methylation
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31510-1