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Impact of mutations in DNA methylation modification genes on genome-wide methylation landscapes and downstream gene activations in pan-cancer
DC Field | Value | Language |
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dc.contributor.author | Lee, Chai-Jin | - |
dc.contributor.author | Ahn, Hongryul | - |
dc.contributor.author | Jeong, Dabin | - |
dc.contributor.author | Pak, Minwoo | - |
dc.contributor.author | Moon, Ji Hwan | - |
dc.contributor.author | Kim, Sun | - |
dc.date.accessioned | 2020-08-13T08:51:28Z | - |
dc.date.available | 2023-05-10T10:54:53Z | - |
dc.date.issued | 2020-02-24 | - |
dc.identifier.citation | BMC Medical Genomics, 13(Suppl 3):27 | ko_KR |
dc.identifier.issn | 1755-8794 | - |
dc.identifier.uri | https://hdl.handle.net/10371/168725 | - |
dc.description.abstract | In cancer, mutations of DNA methylation modification genes have crucial roles for epigenetic modifications genome-wide, which lead to the activation or suppression of important genes including tumor suppressor genes. Mutations on the epigenetic modifiers could affect the enzyme activity, which would result in the difference in genome-wide methylation profiles and, activation of downstream genes. Therefore, we investigated the effect of mutations on DNA methylation modification genes such as DNMT1, DNMT3A, MBD1, MBD4, TET1, TET2 and TET3 through a pan-cancer analysis.
First, we investigated the effect of mutations in DNA methylation modification genes on genome-wide methylation profiles. We collected 3,644 samples that have both of mRNA and methylation data from 12 major cancer types in The Cancer Genome Atlas (TCGA). The samples were divided into two groups according to the mutational signature. Differentially methylated regions (DMR) that overlapped with the promoter region were selected using minfi and differentially expressed genes (DEG) were identified using EBSeq. By integrating the DMR and DEG results, we constructed a comprehensive DNA methylome profiles on a pan-cancer scale. Second, we investigated the effect of DNA methylations in the promoter regions on downstream genes by comparing the two groups of samples in 11 cancer types. To investigate the effects of promoter methylation on downstream gene activations, we performed clustering analysis of DEGs. Among the DEGs, we selected highly correlated gene set that had differentially methylated promoter regions using graph based sub-network clustering methods. We chose an up-regulated DEGs cluster where had hypomethylated promoter in acute myeloid leukemia (LAML) and another down-regulated DEGs cluster where had hypermethylated promoter in colon adenocarcinoma (COAD). To rule out effects of gene regulation by transcription factor (TF), if differentially expressed TFs bound to the promoter of DEGs, that DEGs did not included to the gene set that effected by DNA methylation modifiers. Consequently, we identified 54 hypomethylated promoter DMR up-regulated DEGs in LAML and 45 hypermethylated promoter DMR down-regulated DEGs in COAD. Our study on DNA methylation modification genes in mutated vs. non-mutated groups could provide useful insight into the epigenetic regulation of DEGs in cancer. | ko_KR |
dc.description.sponsorship | This research is supported by National Research Foundation of Korea (NRF)
funded by the Ministry of Science, ICT (No. NRF-2017M3C4A7065887), the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) (No. NRF-2014M3C9A3063541), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3224). The funding bodies provided financial support but had no other role in the design of the study, data collection, analysis, and interpretation of data, decision to publish, or preparation of the manuscript. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | DNA methylation modifier | - |
dc.subject | Sub-network clustering | - |
dc.subject | DMR-DEG integration | - |
dc.subject | Pan-cancer analysis | - |
dc.subject | Genome-wide landscape | - |
dc.title | Impact of mutations in DNA methylation modification genes on genome-wide methylation landscapes and downstream gene activations in pan-cancer | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 이재진 | - |
dc.contributor.AlternativeAuthor | 안홍렬 | - |
dc.contributor.AlternativeAuthor | 정다빈 | - |
dc.contributor.AlternativeAuthor | 박민우 | - |
dc.contributor.AlternativeAuthor | 문지환 | - |
dc.contributor.AlternativeAuthor | 김선 | - |
dc.identifier.doi | 10.1186/s12920-020-0659-4 | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-06-17T13:09:59Z | - |
dc.citation.endpage | 40 | ko_KR |
dc.citation.number | Suppl 3 | ko_KR |
dc.citation.startpage | 27 | ko_KR |
dc.citation.volume | 13 | ko_KR |
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