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Non-small Cell Lung Cancer Epigenomes Exhibit Altered DNA Methylation in Smokers and Neversmokers

Genomics, Proteomics & Bioinformatics 2023年第5期21卷 991-1013页

作者： Jennifer A.Karlow Erica C.Pehrsson Xiaoyun Xing Mark Watson Siddhartha Devarakonda ramaswamy govindan Ting Wang Department of Genetics Washington University School of MedicineSt.LouisMO 63110USA The Edison Family Center for Genome Sciences and Systems Biology Washington University School of MedicineSt.LouisMO 63110USA Department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63110USA Department of Medicine Washington University School of MedicineSt.LouisMO 63110USA McDonnell Genome Institute Washington University School of MedicineSt.LouisMO 63108USA

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment *** 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 *** example,never-smokers displayed a greater proportion of hypomethylated differentially methylated regions(hypoDMRs)and a greater number of recurrently hypomethylated promoters,including those of ASPSCRI,TOP2A,DPP9,and USP39,all previously linked to *** outside of promoters were also widespread and often recurrent,particularly methylation loss over repetitive elements,highly enriched for ERV1 *** hypoDMRs were enriched for several transcription factor binding motifs,often for genes involved in signaling and cell *** example,71%of recurrent promoter hypoDMRs contained a motif for ***,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.

关键词： Non-small cell lung cancer Epigenomics M&M methylCRF DNA methylation

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表皮生长因子/HER2抑制剂在非小细胞肺癌患者治疗中的作用综述

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中国肺癌杂志 2010年第4期13卷 363-369页

作者： ramaswamy govindan 南娟丁燕 Alvin J.Siteman Cancer Center Washington University School of Medicine 天津医科大学总医院天津市肺癌研究所天津市肺癌转移与肿瘤微环境重点实验室

晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)仍然是主要的全球健康问题。尽管可逆性表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂厄洛替尼可改善复发与再发NSCLC患者的生存期,但也存在明显的局限... 详细信息

晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)仍然是主要的全球健康问题。尽管可逆性表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂厄洛替尼可改善复发与再发NSCLC患者的生存期,但也存在明显的局限性,包括仅对少数患者亚群具有临床疗效、生存率较低及产生耐药性。EGFR和HER2的非可逆性抑制剂是临床开发的新型药物,有可能预防并克服第一代EGFR抑制剂的获得性耐药。

关键词： BIBW 2992 ErbB 厄洛替尼吉非替尼 HKI-272 受体酪氨酸激酶

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