Abstract
Despite enormous progress in molecular analysis of cancer cell genomes, the mechanism of tumorigenesis remains unclear. The information present in the genome is not limited to the DNA sequence itself. Indeed, a significant portion of this information is concealed in the spatial structure of chromatin. Ongoing scientific studies that focus on the three-dimensional structure of chromatin raise hopes of arriving at a general explanation of the cancer transformation phenomenon.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
[1] Porta-Pardo E, Kamburov A, Tamborero D, Pons T, Grases D, Valencia A, et al. Comparison of algorithms for the detection of cancer drivers at subgene resolution. Nat Methods 2017;14:782–8.10.1038/nmeth.4364Search in Google Scholar PubMed PubMed Central
[2] Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature 2017;541:359–64.10.1038/nature20788Search in Google Scholar PubMed
[3] Lan X, Jörg DJ, Cavalli FM, Richards LM, Nguyen LV, Vanner RJ, et al. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy. Nature 2017;549:227–32.10.1038/nature23666Search in Google Scholar PubMed PubMed Central
[4] Smith MP, Harper DA. Causes of the Cambrian explosion. Science 2013;341:1355–6.10.1126/science.1239450Search in Google Scholar PubMed
[5] Piwowar M, Dygut J, Piwowar P, Konieczny L, Roterman I. Attempt at a systemic outlook on aging and carcinogenesis. BAMS 2014;19:101–15.10.1515/bams-2014-0012Search in Google Scholar
[6] Pollack RE, Teebor GW. Relationship of contact inhibition to tumor transplantability, morphology, and growth rate. Cancer Res 1969;29:1770–2.Search in Google Scholar PubMed
[7] GTEx Consortium; Laboratory, Data Analysis & Coordinating Center (LDACC) – Analysis Working Group; Statistical Methods groups – Analysis Working Group; Enhancing GTEx (eGTEx) groups; NIH Common Fund; NIH/NCI; et al. Genetic effects on gene expression across human tissues. Nature 2017;550:204–13.10.1038/nature24277Search in Google Scholar PubMed PubMed Central
[8] Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature 2015;526:700–4.10.1038/nature14980Search in Google Scholar PubMed PubMed Central
[9] de Lange T. Activation of telomerase in a human tumor. Proc Natl Acad Sci U S A 1994;91:2882–5.10.1073/pnas.91.8.2882Search in Google Scholar PubMed PubMed Central
[10] Shay JW, Reddel RR, Wright WE. Cancer and telomeres – an ALTernative to telomerase. Science 2012;336:1388–90.10.1126/science.1222394Search in Google Scholar PubMed
[11] Elsässer SJ, Allis CD, Lewis PW. Cancer. New epigenetic drivers of cancers. Science 2011;331:1145–6.10.1126/science.1203280Search in Google Scholar PubMed
[12] Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029–33.10.1126/science.1160809Search in Google Scholar PubMed PubMed Central
[13] Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010;329:1492–9.10.1126/science.1188015Search in Google Scholar PubMed PubMed Central
[14] Turner KM, Deshpande V, Beyter D, Koga T, Rusert J, Lee C, et al. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature 2017;543:122–5.10.1038/nature21356Search in Google Scholar PubMed PubMed Central
[15] Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 2014;505:495–501.10.1038/nature12912Search in Google Scholar PubMed PubMed Central
[16] Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013;502:333–9.10.1038/nature12634Search in Google Scholar PubMed PubMed Central
[17] Weinstein JN, Akbani R, Broom BM, Wang W, Verhaak RG, McConkey D, et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014;507:315–22.10.1038/nature12965Search in Google Scholar PubMed PubMed Central
[18] Tamborero D, Gonzalez-Perez A, Perez-Llamas C, Deu-Pons J, Kandoth C, Reimand J, et al. Comprehensive identification of mutational cancer driver genes across 12 tumor types. Sci Rep 2013;3:2650.10.1038/srep02650Search in Google Scholar PubMed PubMed Central
[19] Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G, et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330–7.10.1038/nature11252Search in Google Scholar PubMed PubMed Central
[20] Tokheim CJ, Papadopoulos N, Kinzler KW, Vogelstein B, Karchin R. Evaluating the evaluation of cancer driver genes. Proc Natl Acad Sci U S A 2016;113:14330–5.10.1073/pnas.1616440113Search in Google Scholar PubMed PubMed Central
[21] Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, et al. Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth. Nature 2015;525:206–11.10.1038/nature15251Search in Google Scholar PubMed PubMed Central
[22] Konieczny L, Roterman I, Spolnik P. Systems biology – strategy of living organism. Heidelberg Dordrecht, London, NY: Springer, 2012.Search in Google Scholar
[23] Ji X, Dadon DB, Powell BE, Fan ZP, Borges-Rivera D, Shachar S, et al. 3D chromosome regulatory landscape of human pluripotent cells. Cell Stem Cell 2016;18:262–75.10.1016/j.stem.2015.11.007Search in Google Scholar PubMed PubMed Central
[24] Davies JO, Telenius JM, McGowan SJ, Roberts NA, Taylor S, Higgs DR, et al. Multiplexed analysis of chromosome conformation at vastly improved sensitivity. Nat Methods 2016;13:74–80.10.1038/nmeth.3664Search in Google Scholar PubMed PubMed Central
[25] Dekker J, Belmont AS, Guttman M, Leshyk VO, Lis JT, Lomvardas S, et al. The 4D nucleome project. Nature 2017;549:219–26.10.1038/nature23884Search in Google Scholar PubMed PubMed Central
[26] Imakaev M, Fudenberg G, McCord RP, Naumova N, Goloborodko A, Lajoie BR, et al. Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat Methods 2012;9:999–1003.10.1038/nmeth.2148Search in Google Scholar PubMed PubMed Central
[27] Dekker J, Marti-Renom MA, Mirny LA. Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat Rev Genet 2013;14:390–403.10.1038/nrg3454Search in Google Scholar PubMed PubMed Central
[28] van Arensbergen J, van Steensel B, Bussemaker HJ. In search of the determinants of enhancer-promoter interaction specificity. Trends Cell Biol 2014;24:695–702.10.1016/j.tcb.2014.07.004Search in Google Scholar PubMed PubMed Central
[29] Nora EP, Dekker J, Heard E. Segmental folding of chromosomes: a basis for structural and regulatory chromosomal neighborhoods? Bioessays 2013;35:818–28.10.1002/bies.201300040Search in Google Scholar PubMed PubMed Central
[30] Sanyal A, Lajoie BR, Jain G, Dekker J. The long-range interaction landscape of gene promoters. Nature 2012;489:109–13.10.1038/nature11279Search in Google Scholar PubMed PubMed Central
[31] Pennisi E. An enhanced view of gene control. Science 2015;348:1407–8.10.1126/science.348.6242.1407Search in Google Scholar PubMed
[32] Terakawa T, Bisht S, Eeftens JM, Dekker C, Haering CH, Greene EC. The condensin complex is a mechanochemical motor that translocates along DNA. Science 2017;358:672–6.10.1126/science.aan6516Search in Google Scholar PubMed PubMed Central
[33] Schwarzer W, Abdennur N, Goloborodko A, Pekowska A, Fudenberg G, Loe-Mie Y, et al. Two independent modes of chromatin organization revealed by cohesin removal. Nature 2017;551:51–6.10.1038/nature24281Search in Google Scholar PubMed PubMed Central
[34] Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ, Zhang LN, et al. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 2014;159:374–87.10.1016/j.cell.2014.09.030Search in Google Scholar PubMed PubMed Central
[35] McCord RP. How to build a cohesive genome in 3D. Nature 2017;551:38–40.10.1038/nature24145Search in Google Scholar PubMed
[36] Willis NA, Frock RL, Menghi F, Duffey EE, Panday A, Camacho V, et al. Mechanism of tandem duplication formation in BRCA1-mutant cells. Nature 2017;551:590–5.10.1038/nature24477Search in Google Scholar PubMed PubMed Central
[37] Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V, Schöpflin R, et al. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature 2016;538:265–9.10.1038/nature19800Search in Google Scholar PubMed
[38] Menghi F, Inaki K, Woo X, Kumar PA, Grzeda KR, Malhotra A, et al. The tandem duplicator phenotype as a distinct genomic configuration in cancer. Proc Natl Acad Sci U S A 2016;113:E2373–82.10.1073/pnas.1520010113Search in Google Scholar PubMed PubMed Central
[39] Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 2015;161:1012–25.10.1016/j.cell.2015.04.004Search in Google Scholar PubMed PubMed Central
[40] Hnisz D, Weintraub AS, Day DS, Valton AL, Bak RO, Li CH, et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science 2016;351:1454–8.10.1126/science.aad9024Search in Google Scholar PubMed PubMed Central
[41] Ferguson-Smith M. Essential medical genetics. Oxford: Blackwell Science, 1997.Search in Google Scholar
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