@article{c552dc5baacf480eb20804ba9ec6b927,
title = "Multi-modal molecular programs regulate melanoma cell state",
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.",
author = "Andrews, {Miles C.} and Junna Oba and Wu, {Chang Jiun} and Haifeng Zhu and Tatiana Karpinets and Creasy, {Caitlin A.} and Forget, {Marie Andr{\'e}e} and Xiaoxing Yu and Xingzhi Song and Xizeng Mao and Robertson, {A. Gordon} and Gabriele Romano and Peng Li and Burton, {Elizabeth M.} and Yiling Lu and Sloane, {Robert Szczepaniak} and Wani, {Khalida M.} and Kunal Rai and Lazar, {Alexander J.} and Haydu, {Lauren E.} and Bustos, {Matias A.} and Jianjun Shen and Yueping Chen and Morgan, {Margaret B.} and Wargo, {Jennifer A.} and Kwong, {Lawrence N.} and Haymaker, {Cara L.} and Grimm, {Elizabeth A.} and Patrick Hwu and Hoon, {Dave S.B.} and Jianhua Zhang and Gershenwald, {Jeffrey E.} and Davies, {Michael A.} and Futreal, {P. Andrew} and Chantale Bernatchez and Woodman, {Scott E.}",
note = "Funding Information: M.C.A. reports advisory board participation, honoraria and research funding to institution from Merck Sharp and Dohme, and contract research for BMS Australia, all outside the submitted work. M.C.A. and J.A.W. are co-inventors on patent applications “Methods and compositions for treating cancer” (WO2020106983A1) and “Methods for improving sex-dimorphic responses to targeted therapy in melanoma” (US20200164034A1), unrelated to the current work. M.A.D. has been a consultant to Roche/Genentech, Array, Pfizer, Novartis, BMS, GSK, Sanofi-Aventis, Vaccinex, Apexigen, and ABM Therapeutics, and has been the PI of research grants to MD Anderson by Roche/Genentech, GSK, Sanofi-Aventis, Merck, Myriad and Oncothyreon. J.A.W. is an inventor on patent applications submitted by the University of Texas MD Anderson Cancer Center “Methods for enhancing immune checkpoint blockade therapy by modulating the microbiome” (PCT/US17/53.717) and “Targeting B cells to enhance response to immune checkpoint blockade” (UTSC.P1412US.P1-MDA19-023); reports compensation for speaker{\textquoteright}s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune and Bristol-Myers Squibb; serves as a consultant/advisory board member for Roche/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, and Ella Therapeutics. AJL reports personal fees from Merck, Bristol-Myers Squibb, Novartis, and Roche/Genentech; personal fees and non-financial support from ArcherDX and Beta-Cat; grants and non-financial support from Medimmune/AstraZeneca and Sanofi; and grants, personal fees and non-financial support from Janssen, all outside the submitted work. J.E.G. reports consulting and/or advisory roles to Merck, Novartis, Syndax, Bristol-Myers Squibb, Regeneron, unrelated to this work. P.H. reports consulting/advisory roles for Dragonfly, Immatics, GSK, and Sanofi. C.B. reports consulting for and receiving funding from Iovance Biotherapeutics and Obsidian Therapeutics as well as serving as a consultant/advisory board member for Myst Therapeutics and Turnstone Biologics. All other authors report no relevant disclosures. Funding Information: This study was supported through a National Health and Medical Research Council of Australia CJ Martin Early Career Fellowship (MCA, #1148680); a Developmental Research Project Award, National Institutes of Health/NCI Cancer Center Support Grant (No. P30 CA016672; S.E.W. and C.B.); NIH R50 Grant (#R50CA221675; Y.L.); The University of Texas MD Anderson Cancer Center Melanoma Moon Shot Program (S.E.W., C.B., A.J.L., J.A.W., J.E.G., M.A.D.); a Faculty Award (SEW); a Rising Stars Award, The University of Texas System (S.E.W.); The University of Texas MD Anderson Cancer Center NCI SPORE in Melanoma (S.E.W., P50 CA093459); Dr Miriam and Sheldon G. Adelson Medical Research Foundation (D.S.B.H., E.A.G., P.H., M.A.D.); AIM at Melanoma Foundation (E.A.G., M.A.D.); the Miriam and Jim Mulva Foundation (E.A.G.); a Cancer Prevention and Research Institute of Texas (CPRIT) Core Facilities Support Award (J.S., CPRIT RP170002); The University of Texas MD Anderson Cancer Center Support grant (NIH/NCI P30 CA016672),; generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shots Program from the Lyda Hill Foundation; and utilized platform assistance from the Cancer Genomics Laboratory and Immunotherapy Platform. Additional support was provided from the Cancer Prevention Research Institute of Texas (R1205 01 to P.A.F.) and Welch Foundation (G-0040 to P.A.F.). MAD receives research support from the National Institutes of Health and National Cancer Institute (NIH/NCI)(1 P50 CA221703-02), the American Cancer Society and the Melanoma Research Alliance, Cancer Fighters of Houston, the Anne and John Mendelsohn Chair for Cancer Research. J.E.G. also receives support from the Robert and Lynne Grossman Family Foundation and the Michael and Patricia Booker Melanoma Research Endowment. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-31510-1",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
