Pan-Cancer Analysis Reveals Differential Susceptibility of Bidirectional Gene Promoters to DNA Methylation, Somatic Mutations, and Copy Number Alterations
Abstract
:1. Introduction
2. Results
2.1. DNA Methylation
2.2. Simple Somatic Mutations
2.3. Somatic Copy Number Alterations
2.4. Cancer Genes
2.5. DNAse Hypersensitive Sites
2.6. Functional Enrichment
3. Discussion
4. Materials and Methods
4.1. Promoter Identification and Definitions
4.2. DNA Methylation Data
4.3. Simple Somatic Mutation Data
4.4. Somatic Copy Number Alteration Data
Author Contributions
Funding
Conflicts of Interest
References
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Cancer | Methylation Matched Tumor and Normal Samples | Promoter Probes | Copy Number Samples |
---|---|---|---|
Bladder Urothelial Carcinoma | 21 | 37,532 | 412 |
Breast Invasive Carcinoma | 96 | 37,124 | 1094 |
Colorectal Adenocarcinoma | 37 | 37,088 | 614 |
Esophogeal Carcinoma | 16 | 37,324 | 184 |
Head & Neck Squamous Cell Carcinoma | 50 | 37,303 | 517 |
Kidney Renal Clear Cell Carcinoma | 160 | 37,325 | 530 |
Kidney Papillary Carcinoma | 45 | 37,227 | 290 |
Hepatocellular Carcinoma | 49 | 36,845 | 375 |
Lung Adenocarcinoma | 32 | 37,082 | 518 |
Lung Small Cell Carcinoma | 42 | 37,581 | 503 |
Pancreatic Adenocarcinoma | 10 | 37,365 | 184 |
Prostate Adenocarcinoma | 50 | 37,416 | 497 |
Thyroid Carcinoma | 56 | 37,779 | 505 |
Uterine Corpus Endometrial Carcinoma | 46 | 37,296 | 540 |
Cancer | ICGC Project Code | Samples | Countries |
---|---|---|---|
Chronic Lymphocytic Leukemia (ES) | CLLE-ES | 201 | Spain |
Ductal Breast Carcinoma (EU/UK) | BRCA-EU | 560 | European Union, United Kingdom |
Esophageal Adenocarcinoma (UK) | ESAD-UK | 203 | United Kingdom |
Ewing Sarcoma (FR) | BOCA-FR | 98 | France |
Malignant Lymphoma (DE) | MALY-DE | 100 | Germany |
Ovarian Serous Cystadenocarcinoma (AU) | OV-AU | 93 | Australia |
Pancreatic Adenocarcinoma (AU) | PACA-AU | 252 | Australia |
Pancreatic Adenocarcinoma (CA) | PACA-CA | 259 | Canada |
Pediatric Brain Cancer (DE) | PBCA-DE | 380 | Germany |
Prostate Adenocarcinoma (CA) | PRAD-CA | 124 | Canada |
Prostate Adenocarcinoma (UK) | PRAD-UK | 108 | United Kingdom |
Renal Cell Carcinoma (EU/FR) | RECA-EU | 95 | European Union, France |
Tissue Type | Promoter Type | Odds Ratio | 95% CI | p-Value |
---|---|---|---|---|
Breast | C/C Bidirectional | 23.73 | [18.72, 30.43] | <2.20 × 10−16 |
C/N Bidirectional | 6.21 | [4.27, 9.15] | <2.20 × 10−16 | |
Pancreas | C/C Bidirectional | 28.36 | [21.53, 38.02] | <2.20 × 10−16 |
C/N Bidirectional | 6.53 | [4.41, 9.86] | <2.20 × 10−16 | |
Placenta | C/C Bidirectional | 23.05 | [18.30, 29.30] | <2.20 × 10−16 |
C/N Bidirectional | 7.02 | [4.80, 10.41] | <2.20 × 10−16 | |
Ovary | C/C Bidirectional | 33.60 | [23.38, 43.66] | <2.20 × 10−16 |
C/N Bidirectional | 10.42 | [6.60, 17.14] | <2.20 × 10−16 |
Pathway | GO ID | Total | Observed | Expected | Ratio | adjP |
---|---|---|---|---|---|---|
DNA metabolic process | GO:0006259 | 899 | 138 | 63.98 | 2.16 | 0.00 × 100 |
RNA processing | GO:0006396 | 851 | 130 | 60.56 | 2.15 | 0.00 × 100 |
DNA repair | GO:0006281 | 472 | 87 | 33.59 | 2.59 | 3.11 × 10−13 |
chromosome organization | GO:0051276 | 562 | 95 | 39.99 | 2.38 | 2.33 × 10−12 |
ncRNA metabolic process | GO:0034660 | 535 | 91 | 38.07 | 2.39 | 5.41 × 10−12 |
ncRNA processing | GO:0034470 | 379 | 68 | 26.97 | 2.52 | 1.29 × 10−9 |
cellular response to DNA damage stimulus | GO:0006974 | 731 | 104 | 52.02 | 2 | 5.60 × 10−9 |
organelle fission | GO:0048285 | 578 | 84 | 41.13 | 2.04 | 2.10 × 10−7 |
mitochondrion organization | GO:0007005 | 599 | 86 | 42.63 | 2.02 | 2.10 × 10−7 |
cell cycle | GO:0007049 | 1591 | 178 | 113.22 | 1.57 | 2.10 × 10−7 |
double-strand break repair | GO:0006302 | 181 | 39 | 12.88 | 3.03 | 2.39 × 10−7 |
nuclear division | GO:0000280 | 537 | 79 | 38.21 | 2.07 | 2.87 × 10−7 |
cell cycle process | GO:0022402 | 1217 | 143 | 86.61 | 1.65 | 4.92 × 10−7 |
DNA recombination | GO:0006310 | 244 | 46 | 17.36 | 2.65 | 5.42 × 10−7 |
telomere maintenance | GO:0000723 | 119 | 29 | 8.47 | 3.42 | 1.69 × 10−6 |
telomere organization | GO:0032200 | 122 | 29 | 8.68 | 3.34 | 2.94 × 10−6 |
DNA conformation change | GO:0071103 | 235 | 43 | 16.72 | 2.57 | 4.03 × 10−6 |
nucleic acid phosphodiester bond hydrolysis | GO:0090305 | 264 | 46 | 18.79 | 2.45 | 5.68 × 10−6 |
DNA biosynthetic process | GO:0071897 | 187 | 36 | 13.31 | 2.71 | 1.53 × 10−5 |
rRNA metabolic process | GO:0016072 | 250 | 43 | 17.79 | 2.42 | 2.25 × 10−5 |
ribonucleoprotein complex biogenesis | GO:0022613 | 420 | 60 | 29.89 | 2.01 | 6.35 × 10−5 |
mitotic cell cycle process | GO:1903047 | 842 | 100 | 59.92 | 1.67 | 7.95 × 10−5 |
ribosome biogenesis | GO:0042254 | 302 | 47 | 21.49 | 2.19 | 1.07 × 10−4 |
mRNA processing | GO:0006397 | 442 | 61 | 31.45 | 1.94 | 1.49 × 10−4 |
rRNA processing | GO:0006364 | 243 | 40 | 17.29 | 2.31 | 1.72 × 10−4 |
mitotic cell cycle | GO:0000278 | 926 | 106 | 65.9 | 1.61 | 1.76 × 10−4 |
mitotic nuclear division | GO:0007067 | 411 | 57 | 29.25 | 1.95 | 2.70 × 10−4 |
mRNA metabolic process | GO:0016071 | 631 | 78 | 44.9 | 1.74 | 3.11× 10−4 |
chromatin organization | GO:0006325 | 676 | 82 | 48.11 | 1.7 | 3.41 × 10−4 |
tRNA processing | GO:0008033 | 115 | 24 | 8.18 | 2.93 | 4.10 × 10−4 |
DNA synthesis involved in DNA repair | GO:0000731 | 71 | 18 | 5.05 | 3.56 | 4.31 × 10−4 |
mitochondrial translation | GO:0032543 | 117 | 24 | 8.33 | 2.88 | 5.28 × 10−4 |
DNA-templated transcription, termination | GO:0006353 | 94 | 21 | 6.69 | 3.14 | 5.28 × 10−4 |
chromosome segregation | GO:0007059 | 305 | 45 | 21.7 | 2.07 | 5.64 × 10−4 |
cellular macromolecular complex assembly | GO:0034622 | 876 | 99 | 62.34 | 1.59 | 5.64 × 10−4 |
protein folding | GO:0006457 | 204 | 34 | 14.52 | 2.34 | 6.34 × 10−4 |
regulation of chromosome organization | GO:0033044 | 128 | 25 | 9.11 | 2.74 | 7.25 × 10−4 |
regulation of organelle organization | GO:0033043 | 963 | 106 | 68.53 | 1.55 | 7.58 × 10−4 |
DNA packaging | GO:0006323 | 155 | 28 | 11.03 | 2.54 | 9.00 × 10−4 |
mitochondrial translational elongation | GO:0070125 | 83 | 19 | 5.91 | 3.22 | 9.01 × 10−4 |
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Thompson, J.A.; Christensen, B.C.; Marsit, C.J. Pan-Cancer Analysis Reveals Differential Susceptibility of Bidirectional Gene Promoters to DNA Methylation, Somatic Mutations, and Copy Number Alterations. Int. J. Mol. Sci. 2018, 19, 2296. https://doi.org/10.3390/ijms19082296
Thompson JA, Christensen BC, Marsit CJ. Pan-Cancer Analysis Reveals Differential Susceptibility of Bidirectional Gene Promoters to DNA Methylation, Somatic Mutations, and Copy Number Alterations. International Journal of Molecular Sciences. 2018; 19(8):2296. https://doi.org/10.3390/ijms19082296
Chicago/Turabian StyleThompson, Jeffrey A., Brock C. Christensen, and Carmen J. Marsit. 2018. "Pan-Cancer Analysis Reveals Differential Susceptibility of Bidirectional Gene Promoters to DNA Methylation, Somatic Mutations, and Copy Number Alterations" International Journal of Molecular Sciences 19, no. 8: 2296. https://doi.org/10.3390/ijms19082296