دورية أكاديمية
Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures
| العنوان: | Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures |
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| المؤلفون: | Graham, Nicholas A., Minasyan, Aspram, Lomova, Anastasia, Cass, Ashley, Balanis, Nikolas G., Friedman, Michael, Chan, Shawna, Zhao, Sophie, Delgado, Adrian, Go, James, Beck, Lillie, Hurtz, Christian, Ng, Carina, Qiao, Rong, ten Hoeve, Johanna, Palaskas, Nicolaos, Wu, Hong, Muschen, Markus, Multani, Asha S., Port, Elisa, Larson, Steven M., Schultz, Nikolaus, Braas, Daniel, Christofk, Heather R., Mellinghoff, Ingo K., Graeber, Thomas G. |
| المساهمون: | Graeber, TG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA., Graeber, TG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA., Univ Calif Los Angeles, David Geffen Sch Med, Crump Inst Mol Imaging, Los Angeles, CA 90095 USA., Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA., Univ Southern Calif, Mork Family Dept Chem Engn & Mat Sci, Los Angeles, CA USA., Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA., Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA., Peking Univ, Sch Life Sci, Beijing, Peoples R China., Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China., Univ Cambridge, Dept Haematol, Cambridge, England., Univ Texas Houston, MD Anderson Canc Ctr, Dept Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA., Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA., Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA., Mem Sloan Kettering Canc Ctr, Marie Josee & Henry R Kravis Ctr Mol Oncol, 1275 York Ave, New York, NY 10021 USA., Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA., Univ Calif Los Angeles, David Geffen Sch Med, Metabol Ctr, Los Angeles, CA 90095 USA., Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA., Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA., Weill Cornell Med Coll, Dept Neurol, New York, NY USA., Univ Calif Los Angeles, David Geffen Sch Med, Calif NanoSyst Inst, Los Angeles, CA 90095 USA., Univ Penn, Dept Med, Div Hematol & Oncol, Philadelphia, PA 19104 USA. |
| المصدر: | SCI |
| بيانات النشر: | MOLECULAR SYSTEMS BIOLOGY |
| سنة النشر: | 2017 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | aneuploidy, DNA copy number alterations, genomic instability, glycolysis, metabolism, CANCER CELL-LINES, BREAST-CANCER, GLUCOSE-METABOLISM, INITIATING CELLS, MOUSE MODELS, MOLECULAR CLASSIFICATION, PYRUVATE-DEHYDROGENASE, LUNG-CANCER, LIFE-SPAN, KEY ROLE |
| الوصف: | Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including F-18-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p(53) mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes. A pan-cancer and cross-species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer-driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution. ; National Institutes of Health [P30 CA016042, 5P30 AI028697]; JCCC; UCLA AIDS Institute; David Geffen School of Medicine at UCLA; UCLA Chancellor's Office; UCLA Vice Chancellor's Office of Research; UCLA Scholars in Oncologic Molecular Imagining Program (NCI/NIH grant) [R25T CA098010]; UCLA Eugene V. Cota-Robles Fellowship; UCLA Dissertation Year Fellowship; NCI/NIH [P50 CA086438, P01 CA168585, P50 CA086306, U19 AI06776]; American Cancer Society Research Scholar Award [RSG-12-257-01-TBE]; Melanoma ... |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1744-4292 |
| العلاقة: | MOLECULAR SYSTEMS BIOLOGY.2017,13(2).; 1909968; http://hdl.handle.net/20.500.11897/475446Test; WOS:000393981300005 |
| DOI: | 10.15252/msb.20167159 |
| الإتاحة: | https://doi.org/20.500.11897/475446Test https://doi.org/10.15252/msb.20167159Test https://hdl.handle.net/20.500.11897/475446Test |
| رقم الانضمام: | edsbas.E389A424 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17444292 |
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| DOI: | 10.15252/msb.20167159 |