Title | The association between copy number aberration, DNA methylation and gene expression in tumor samples. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Sun, Wei, Paul Bunn, Chong Jin, Paul Little, Vasyl Zhabotynsky, Charles M. Perou, David Neil Hayes, Mengjie Chen, and Dan-Yu Lin |
Journal | Nucleic Acids Res |
Volume | 46 |
Issue | 6 |
Pagination | 3009-3018 |
Date Published | 2018 Apr 06 |
ISSN | 1362-4962 |
Keywords | Breast Neoplasms, Colonic Neoplasms, CpG Islands, Databases, Genetic, DNA Copy Number Variations, DNA Methylation, Female, Gene Expression Regulation, Neoplastic, Glioblastoma, Glioma, Humans, Leukemia, Male, Prostatic Neoplasms |
Abstract | We systematically studied the association between somatic copy number aberration (SCNA), DNA methylation and gene expression using -omic data from The Cancer Genome Atlas (TCGA) on six cancer types: breast cancer, colon cancer, glioblastoma, leukemia, lower-grade glioma and prostate cancer. A major challenge for such integrated study is that the association between DNA methylation and gene expression is severely confounded by tumor purity and cell type composition, which are often unobserved and difficult to estimate. To overcome this challenge, we developed a method to remove confounding effects by calculating the principal components that span the space of the latent factors. Another intriguing findings of our study is that there could be both positive and negative associations between SCNA and DNA methylation, while the CpGs with negative/positive associations with SCNA are often located around CpG islands/ocean, respectively. A joint study of SCNA, DNA methylation, and gene expression suggest that SCNA often affect DNA methylation and gene expression independently. |
DOI | 10.1093/nar/gky131 |
Alternate Journal | Nucleic Acids Res |
Original Publication | The association between copy number aberration, DNA methylation and gene expression in tumor samples. |
PubMed ID | 29529299 |
PubMed Central ID | PMC5887505 |
Grant List | R01 GM105785 / GM / NIGMS NIH HHS / United States R01 GM126550 / GM / NIGMS NIH HHS / United States R01 HG009974 / HG / NHGRI NIH HHS / United States R01 GM047845 / GM / NIGMS NIH HHS / United States R01 GM070335 / GM / NIGMS NIH HHS / United States R01 CA189532 / CA / NCI NIH HHS / United States R01 GM126553 / GM / NIGMS NIH HHS / United States S10 OD020069 / OD / NIH HHS / United States P01 CA142538 / CA / NCI NIH HHS / United States |
The association between copy number aberration, DNA methylation and gene expression in tumor samples.
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