首页|Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Never-smokers

Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Never-smokers

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Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome.To determine the potential contribution of DNA methylation alterations to tumor phenotype in non-small cell lung cancer(NSCLC)in both smoker and never-smoker patients,we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays,methylated DNA immunoprecipitation sequencing(MeDIP-seq)and methylation sensitive restric-tion enzyme sequencing(MRE-seq).We reported recurrent methylation changes in the promoters of several genes,many previously implicated in cancer,including FAM83A and SEPT9(hy-pomethylation),as well as PCDH7,NKX2-1,and SOX17(hypermethylation).Although many methylation changes between tumors and their paired normal samples were shared across patients,several were specific to a particular smoking status.For example,never-smokers displayed a greater proportion of hypomethylated differentially methylated regions(hypoDMRs)and a greater number of recurrently hypomethylated promoters,including those of ASPSCR1,TOP2A,DPP9,and USP39,all previously linked to cancer.Changes outside of promoters were also widespread and often recurrent,particularly methylation loss over repetitive elements,highly enriched for ERV1 subfamilies.Recurrent hypoDMRs were enriched for several transcription factor binding motifs,often for genes involved in signaling and cell proliferation.For example,71％of recurrent promoter hypoDMRs contained a motif for NKX2-1.Finally,the majority of DMRs were located within an active chromatin state in tissues profiled using the Roadmap Epigenomics data,suggesting that methylation changes may contribute to altered regulatory programs through the adaptation of cell type-specific expression programs.

Non-small cell lung cancerEpigenomicsM&MmethylCRFDNA methylation

Jennifer A.Karlow、Erica C.Pehrsson、Xiaoyun Xing、Mark Watson、Siddhartha Devarakonda、Ramaswamy Govindan、Ting Wang

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Department of Genetics,Washington University School of Medicine,St.Louis,MO 63110,USA

The Edison Family Center for Genome Sciences and Systems Biology,Washington University School of Medicine,St.Louis,MO 63110,USA

Department of Pathology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA 02215, USA

Department of Pathology and Immunology,Washington University School of Medicine,St.Louis,MO 63110,USA

Department of Medicine,Washington University School of Medicine,St.Louis,MO 63110,USA

McDonnell Genome Institute,Washington University School of Medicine,St.Louis,MO 63108,USA

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Siteman Cancer Center Precision Medicine Pathwaya Postdoctoral Fellowship from the American Cancer SocietyNational Institutes of Health(National Human Genome Research Institute)National Institutes of Health(National Human Genome Research Institute)National Institutes of Health(National Human Genome Research Institute)National Institutes of Health(National Institute of Environmental Health Sciences)National Institutes of Health(National Institute of Environmental Health Sciences)National Institutes of Health(National Cancer Institute)American Cancer Society

T32CA113275PF-17-201-01R01HG007354R01HG007175U01HG009391R01ES024992U24ES026699U01CA200060RSG-14-049-01-DMC

2023

10.1016/j.gpb.2023.03.006

基因组蛋白质组与生物信息学报(英文版)
中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)

CSTPCDCSCD
影响因子：0.495
ISSN：1672-0229
年,卷(期)：2023.21(5)
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