@article{a15f033464914b04958c7510bb521aa4,
title = "Integrative epigenomic analyses of small cell lung cancer cells demonstrates the clinical translational relevance of gene body methylation",
abstract = "DNA methylation is a key regulator of gene expression and a clinical therapeutic predictor. We examined global DNA methylation beyond the generally used promoter areas in human small cell lung cancer (SCLC) and find that gene body methylation is a robust positive predictor of gene expression. Combining promoter and gene body methylation better predicts gene expression than promoter methylation alone including genes involved in the neuroendocrine classification of SCLC and the expression of therapeutically relevant genes including MGMT, SLFN11, and DLL3. Importantly, for super-enhancer (SE) covered genes such as NEUROD1 or MYC, using H3K27ac and NEUROD1, ASCL1, and POU2F3 ChIP-seq data, we show that genic methylation is inversely proportional to expression, thus providing a new approach to identify potential SE regulated genes involved in SCLC pathogenesis. To advance SCLC transitional research, these data are integrated into our web portal (https://discover.nci.nih.gov/SclcCellMinerCDB/) for open and easy access to basic and clinical investigators.",
keywords = "Cancer, Cancer systems biology, Epigenetics",
author = "Pongor, {Lorinc S.} and Camille Tlemsani and Fathi Elloumi and Yasuhiro Arakawa and Ukhyun Jo and Gross, {Jacob M.} and Sara Mosavarpour and Sudhir Varma and Kollipara, {Rahul K.} and Nitin Roper and Teicher, {Beverly A.} and Aladjem, {Mirit I.} and William Reinhold and Anish Thomas and Minna, {John D.} and Johnson, {Jane E.} and Yves Pommier",
note = "Funding Information: The studies performed by NCI members are supported by the Center for Cancer Research, the Intramural Program of the US National Cancer Institute, National Institutes of Health (Z01 BC 006150, ZIA BC010411). Grant support for JDM, JEJ. U01 CA213338, U24 CA213274, P50 CA070907. This work utilized the computational resources of the NIH HPC Biowulf cluster. (http://hpc.nih.gov). Conceptualization, L.S.P. C.T. B.A.T, M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P.; Methodology, L.S.P. C.T. B.A.T, M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P.; Software, L.S.P. C.T. F.E. Y.A, U.J. J.M.G, S.M. S.V. R.K.K. N.R. B.A.T, M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P; Formal Analysis, L.S.P. C.T. F.E. Y.A, U.J. J.M.G, S.M. S.V. R.K.K. N.R. B.A.T, M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P.; Data Curation, L.S.P. C.T. F.E. S.V. M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P.; Writing – Original Draft, L.S.P. C.T. M.I.A. W.R. A.T. J.D.M, J.E.J, and Y.P; Writing – Review & Editing, L.S.P. C.T. F.E. Y.A. U.J. J.M.J, S.M. S.V. R.K.K. N.R. B.A.T. M.I.A, W.R. A.T. J.D.M. J.E.J. and Y.P. The authors declare no competing interests. JDM receives royalties from the NCI and UT Southwestern Medical Center for the distribution of human tumor cell lines. Funding Information: The studies performed by NCI members are supported by the Center for Cancer Research , the Intramural Program of the US National Cancer Institute , National Institutes of Health ( Z01 BC 006150 , ZIA BC010411 ). Grant support for JDM , JEJ. U01 CA213338 , U24 CA213274 , P50 CA070907 . This work utilized the computational resources of the NIH HPC Biowulf cluster. ( http://hpc.nih.gov ). Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = nov,
day = "18",
doi = "10.1016/j.isci.2022.105338",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "11",
}