论文库首页  论文库
 
论文编号:
论文题目: Epigenetic and genetic deregulation in cancer target distinct signaling pathway domains
英文论文题目: Epigenetic and genetic deregulation in cancer target distinct signaling pathway domains
第一作者: Gao, Y; Teschendorff, AE
英文第一作者: Gao, Y; Teschendorff, AE
联系作者: Teschendorff, AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Teschendorff, AE (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 45
期: 2
页码: 583-596
摘要: Cancer is characterized by both genetic and epigenetic alterations. While cancer driver mutations and copy-number alterations have been studied at a systems-level, relatively little is known about the systems-level patterns exhibited by their epigenetic counterparts. Here we perform a pan-cancer wide systems-level analysis, mapping candidate cancerdriver DNA methylation (DNAm) alterations onto a human interactome. We demonstrate that functional DNAm alterations in cancer tend to map to nodes of lower connectivity and inter-connectivity, compared to the corresponding alterations at the genomic level. We find that epigenetic alterations are relatively over-represented in extracellular and transmembrane signaling domains, whereas cancer genes undergoing amplification or deletion tend to be enriched within the intracellular domain. A pan-cancer wide meta-analysis identifies WNT and chemokine signaling, as two key pathways where epigenetic deregulation preferentially targets extracellular components. We further pinpoint specific chemokine ligands/receptors whose epigenetic deregulation associates with key epigenetic enzymes, representing potential targets for epigenetic therapy. Our results suggest that epigenetic deregulation in cancer not only targets tissue-specific transcription factors, but also modulates signaling within the extra-cellular domain, providing novel system-level insight into the potential distinctive role of genetic and epigenetic alterations in cancer.
英文摘要: Cancer is characterized by both genetic and epigenetic alterations. While cancer driver mutations and copy-number alterations have been studied at a systems-level, relatively little is known about the systems-level patterns exhibited by their epigenetic counterparts. Here we perform a pan-cancer wide systems-level analysis, mapping candidate cancerdriver DNA methylation (DNAm) alterations onto a human interactome. We demonstrate that functional DNAm alterations in cancer tend to map to nodes of lower connectivity and inter-connectivity, compared to the corresponding alterations at the genomic level. We find that epigenetic alterations are relatively over-represented in extracellular and transmembrane signaling domains, whereas cancer genes undergoing amplification or deletion tend to be enriched within the intracellular domain. A pan-cancer wide meta-analysis identifies WNT and chemokine signaling, as two key pathways where epigenetic deregulation preferentially targets extracellular components. We further pinpoint specific chemokine ligands/receptors whose epigenetic deregulation associates with key epigenetic enzymes, representing potential targets for epigenetic therapy. Our results suggest that epigenetic deregulation in cancer not only targets tissue-specific transcription factors, but also modulates signaling within the extra-cellular domain, providing novel system-level insight into the potential distinctive role of genetic and epigenetic alterations in cancer.
刊物名称: NUCLEIC ACIDS RESEARCH
英文刊物名称: NUCLEIC ACIDS RESEARCH
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 10.162
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有