Cancer Is Associated with Alterations in the Three-Dimensional Organization of the Genome
Abstract
:1. Introduction
2. Results
2.1. A Total of 1467 Topologically Associating Domains (TADs) Constitute the Consensus TAD Map of the Human Genome
2.2. Six Percent of Consensus TADs Are Enriched or Depleted for Cancer-Related CNVs
2.3. TADs Enriched for CNVs Are Valuable Prognostic Biomarkers in Cancer
2.4. Thirty-Four Percent of Prognostic TADs Tend to Undergo Large Structural Changes in Cancer
3. Discussion
4. Materials and Methods
4.1. Topologically Associating Domain (TAD) Maps
4.2. TAD Size Comparison Between Normal and Cancer States
4.3. Similarity Between TAD Maps of Different Tissues/Cell Lines
4.4. Construction of Consensus TADs
4.4.1. Contribution of Each Tissue/Cell Line in Total Gene Expression Divergence
4.4.2. Conservation Scores
4.5. Constitutive and Perturbed TADs
4.6. Enrichment Analysis of CTCF Peaks and Housekeeping Genes (HK Genes) in Consensus TADs and TBRs
4.7. Cancer-Related Copy Number Variants (CNVs)
4.8. TADs Enriched/Depleted for CNVs
4.9. Pan-Cancer Genes
4.10. Functional and Pathway Analysis
4.11. Survival Analysis
4.11.1. TAD- and Pan-Cancer Gene-Based Overall Survival Cox Regression Models
4.11.2. Prognostic TADs and Pan-Cancer Genes
4.11.3. Patient Stratification
4.12. CNV Densities in Constitutive and Perturbed TADs
4.13. Expression Levels of NOCR2 in SARC Patients
4.14. Independent Validation of the OV TAD-Based Model
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Li, L.; Barth, N.K.H.; Pilarsky, C.; Taher, L. Cancer Is Associated with Alterations in the Three-Dimensional Organization of the Genome. Cancers 2019, 11, 1886. https://doi.org/10.3390/cancers11121886
Li L, Barth NKH, Pilarsky C, Taher L. Cancer Is Associated with Alterations in the Three-Dimensional Organization of the Genome. Cancers. 2019; 11(12):1886. https://doi.org/10.3390/cancers11121886
Chicago/Turabian StyleLi, Lifei, Nicolai K. H. Barth, Christian Pilarsky, and Leila Taher. 2019. "Cancer Is Associated with Alterations in the Three-Dimensional Organization of the Genome" Cancers 11, no. 12: 1886. https://doi.org/10.3390/cancers11121886