Skip to main content

Inferring the Cancer Cellular Epigenome Heterogeneity via DNA Methylation Patterns

  • Chapter
  • First Online:
Epigenetics in Oncology

Part of the book series: Cancer Treatment and Research ((CTAR,volume 190))

Abstract

Tumor cells evolve through space and time, generating genetically and phenotypically diverse cancer cell populations that are continually subjected to the selection pressures of their microenvironment and cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Merlo LM, Pepper JW, Reid BJ, Maley CC (2006) Cancer as an evolutionary and ecological process. Nat Rev Cancer 6(12):924–935

    Article  CAS  PubMed  Google Scholar 

  2. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194(4260):23–28

    Article  CAS  PubMed  Google Scholar 

  3. Easwaran H, Tsai HC, Baylin SB (2014) Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell 54(5):716–727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gerlinger M, Swanton C (2010) How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. Br J Cancer 103(8):1139–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Li S, Mason CE, Melnick A (2016) Genetic and epigenetic heterogeneity in acute myeloid leukemia. Curr Opin Genet Dev 36:100–106

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fortunato A, Boddy A, Mallo D, Aktipis A, Maley CC, Pepper JW (2017) Natural selection in cancer biology: from molecular snowflakes to trait hallmarks. Cold Spring Harb Perspect Med 7(2)

    Google Scholar 

  7. Liggett LA, DeGregori J (2017) Changing mutational and adaptive landscapes and the genesis of cancer. Biochim Biophys Acta Rev Cancer 1867(2):84–94

    Article  CAS  PubMed  Google Scholar 

  8. Herceg Z, Hainaut P (2007) Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol 1(1):26–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lu Y, Chan YT, Tan HY, Li S, Wang N, Feng Y (2020) Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer 19(1):79

    Article  PubMed  PubMed Central  Google Scholar 

  10. Laconi E, Marongiu F, DeGregori J (2020) Cancer as a disease of old age: changing mutational and microenvironmental landscapes. Br J Cancer 122(7):943–952

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vendramin R, Litchfield K, Swanton C (2021) Cancer evolution: Darwin and beyond. EMBO J 40(18):e108389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dean JA, Tanguturi SK, Cagney D, Shin KY, Youssef G, Aizer A, et al (2022) Phase I study of a novel glioblastoma radiation therapy schedule exploiting cell-state plasticity. Neuro Oncol

    Google Scholar 

  13. Li S, Garrett-Bakelman FE, Chung SS, Sanders MA, Hricik T, Rapaport F et al (2016) Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med 22(7):792–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pan H, Jiang Y, Boi M, Tabbo F, Redmond D, Nie K et al (2015) Epigenomic evolution in diffuse large B-cell lymphomas. Nat Commun 6:6921

    Article  CAS  PubMed  Google Scholar 

  15. Landau DA, Clement K, Ziller MJ, Boyle P, Fan J, Gu H et al (2014) Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell 26(6):813–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sheffield NC, Pierron G, Klughammer J, Datlinger P, Schonegger A, Schuster M et al (2017) DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nat Med 23(3):386–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu Y, Rosikiewicz W, Pan Z, Jillette N, Wang P, Taghbalout A et al (2021) DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation. Genome Biol 22(1):295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen X, Ashoor H, Musich R, Wang J, Zhang M, Zhang C et al (2021) Epihet for intra-tumoral epigenetic heterogeneity analysis and visualization. Sci Rep 11(1):376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li S, Labaj PP, Zumbo P, Sykacek P, Shi W, Shi L et al (2014) Detecting and correcting systematic variation in large-scale RNA sequencing data. Nat Biotechnol 32(9):888–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li S, Garrett-Bakelman F, Perl AE, Luger SM, Zhang C, To BL et al (2014) Dynamic evolution of clonal epialleles revealed by methclone. Genome Biol 15(9):472

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li S, Garrett-Bakelman FE, Akalin A, Zumbo P, Levine R, To BL, et al (2013) An optimized algorithm for detecting and annotating regional differential methylation. BMC Bioinform 14

    Google Scholar 

  22. Akalin A, Kormaksson M, Li S, Garrett-Bakelman FE, Figueroa ME, Melnick A, et al (2012) methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol 13(10)

    Google Scholar 

  23. Wang L, Wang S, Li W (2012) RSeQC: quality control of RNA-seq experiments. Bioinformatics 28(16):2184–2185

    Article  CAS  PubMed  Google Scholar 

  24. Robinson MD, McCarthy DJ, Smyth GK (2010) EdgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140

    Article  CAS  PubMed  Google Scholar 

  25. Farlik M, Halbritter F, Muller F, Choudry FA, Ebert P, Klughammer J et al (2016) DNA methylation dynamics of human hematopoietic stem cell differentiation. Cell Stem Cell 19(6):808–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wu D, Hu D, Chen H, Shi G, Fetahu IS, Wu F et al (2018) Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer. Nature 559(7715):637–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Thomson JP, Hunter JM, Lempiainen H, Muller A, Terranova R, Moggs JG et al (2013) Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver. Nucleic Acids Res 41(11):5639–5654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sellars M, Huh JR, Day K, Issuree PD, Galan C, Gobeil S et al (2015) Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages. Nat Immunol 16(7):746–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hamerman JA, Page ST, Pullen AM (1997) Distinct methylation states of the CD8 beta gene in peripheral T cells and intraepithelial lymphocytes. J Immunol 159(3):1240–1246

    Article  CAS  PubMed  Google Scholar 

  30. Velychko S, Adachi K, Kim KP, Hou Y, MacCarthy CM, Wu G, et al (2019) Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs. Cell Stem Cell 25(6):737–753 e4

    Google Scholar 

  31. Rosikiewicz W, Chen X, Dominguez PM, Ghamlouch H, Aoufouchi S, Bernard OA, et al (2020) TET2 deficiency reprograms the germinal center B cell epigenome and silences genes linked to lymphomagenesis. Sci Adv 6(25):eaay5872

    Google Scholar 

  32. Dominguez PM, Ghamlouch H, Rosikiewicz W, Kumar P, Beguelin W, Fontan L et al (2018) TET2 deficiency causes germinal center hyperplasia, impairs plasma cell differentiation, and promotes b-cell lymphomagenesis. Cancer Discov 8(12):1632–1653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Roadmap Epigenomics C, Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518(7539):317–330

    Article  Google Scholar 

  34. Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE, Lee AY et al (2015) Chromatin architecture reorganization during stem cell differentiation. Nature 518(7539):331–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hon GC, Song CX, Du T, Jin F, Selvaraj S, Lee AY et al (2014) 5mC oxidation by Tet2 modulates enhancer activity and timing of transcriptome reprogramming during differentiation. Mol Cell 56(2):286–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Moran-Crusio K, Reavie L, Shih A, Abdel-Wahab O, Ndiaye-Lobry D, Lobry C et al (2011) Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20(1):11–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tsagaratou A, Aijo T, Lio CW, Yue X, Huang Y, Jacobsen SE et al (2014) Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation. Proc Natl Acad Sci U S A 111(32):E3306–E3315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J et al (2011) Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell 42(4):451–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sardina JL, Collombet S, Tian TV, Gomez A, Di Stefano B, Berenguer C et al (2018) Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate. Cell Stem Cell 23(6):905–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N (2012) MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 151(7):1417–1430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li S, Chen X, Wang J, Meydan C, Glass JL, Shih AH et al (2020) Somatic mutations drive specific, but reversible, epigenetic heterogeneity states in AML. Cancer Discov 10(12):1934–1949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, et al (2017) Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 356(6337)

    Google Scholar 

  43. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326(5950):289–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO et al (2016) Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529(7584):110–114

    Article  CAS  PubMed  Google Scholar 

  45. Dawson MA (2017) The cancer epigenome: concepts, challenges, and therapeutic opportunities. Science 355(6330):1147–1152

    Article  CAS  PubMed  Google Scholar 

  46. Setty M, Helmy K, Khan AA, Silber J, Arvey A, Neezen F et al (2012) Inferring transcriptional and microRNA-mediated regulatory programs in glioblastoma. Mol Syst Biol 8:605

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lefebvre C, Rajbhandari P, Alvarez MJ, Bandaru P, Lim WK, Sato M et al (2010) A human B-cell interactome identifies MYB and FOXM1 as master regulators of proliferation in germinal centers. Mol Syst Biol 6:377

    Article  PubMed  PubMed Central  Google Scholar 

  48. Wainwright EN, Scaffidi P (2017) Epigenetics and cancer stem cells: unleashing, hijacking, and restricting cellular plasticity. Trends Cancer. 3(5):372–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Toh TB, Lim JJ, Chow EK (2017) Epigenetics in cancer stem cells. Mol Cancer 16(1):29

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S et al (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141(1):69–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Liau BB, Sievers C, Donohue LK, Gillespie SM, Flavahan WA, Miller TE, et al (2017) Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance. Cell Stem Cell 20(2):233–246 e7

    Google Scholar 

  52. Guo Q, Jing FJ, Xu W, Li X, Li X, Sun JL et al (2019) Ubenimex induces autophagy inhibition and EMT suppression to overcome cisplatin resistance in GC cells by perturbing the CD13/EMP3/PI3K/AKT/NF-kappaB axis. Aging (Albany NY) 12(1):80–105

    Article  PubMed  PubMed Central  Google Scholar 

  53. Gaiti F, Chaligne R, Gu H, Brand RM, Kothen-Hill S, Schulman RC et al (2019) Epigenetic evolution and lineage histories of chronic lymphocytic leukemia. Nature 569(7757):576–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Johnson KC, Anderson KJ, Courtois ET, Gujar AD, Barthel FP, Varn FS et al (2021) Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response. Nat Genet 53(10):1456–1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK et al (2017) Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 130(6):722–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Konopleva M, Pollyea DA, Potluri J, Chyla B, Hogdal L, Busman T et al (2016) Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous Leukemia. Cancer Discov 6(10):1106–1117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J et al (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19(2):202–208

    Article  CAS  PubMed  Google Scholar 

  58. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH et al (2020) Azacitidine and venetoclax in previously untreated acute myeloid Leukemia. N Engl J Med 383(7):617–629

    Article  CAS  PubMed  Google Scholar 

  59. Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G et al (2022) Ivosidenib and azacitidine in IDH1-mutated acute myeloid Leukemia. N Engl J Med 386(16):1519–1531

    Article  CAS  PubMed  Google Scholar 

  60. Mattei AL, Bailly N, Meissner A (2022) DNA methylation: a historical perspective. Trends Genet 38(7):676–707

    Article  CAS  PubMed  Google Scholar 

  61. Aran D, Hellman A (2013) DNA methylation of transcriptional enhancers and cancer predisposition. Cell 154(1):11–13

    Article  CAS  PubMed  Google Scholar 

  62. Xu J, Song F, Lyu H, Kobayashi M, Zhang B, Zhao Z et al (2022) Subtype-specific 3D genome alteration in acute myeloid leukemia. Nature 611(7935):387–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gereige LM, Mikkola HK (2009) DNA methylation is a guardian of stem cell self-renewal and multipotency. Nat Genet 41(11):1164–1166

    Article  CAS  PubMed  Google Scholar 

  64. Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P et al (2012) DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol Cell 47(4):633–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ramchandani S, Bhattacharya SK, Cervoni N, Szyf M (1999) DNA methylation is a reversible biological signal. Proc Natl Acad Sci USA 96(11):6107–6112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. McGraw S, Zhang JX, Farag M, Chan D, Caron M, Konermann C et al (2015) Transient DNMT1 suppression reveals hidden heritable marks in the genome. Nucleic Acids Res 43(3):1485–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257

    Article  CAS  PubMed  Google Scholar 

  68. Shih AH, Meydan C, Shank K, Garrett-Bakelman FE, Ward PS, Intlekofer AM et al (2017) Combination targeted therapy to disrupt aberrant oncogenic signaling and reverse epigenetic dysfunction in IDH2- and TET2-mutant acute myeloid leukemia. Cancer Discov 7(5):494–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Shih AH, Jiang Y, Meydan C, Shank K, Pandey S, Barreyro L et al (2015) Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia. Cancer Cell 27(4):502–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov 12(1):31–46

    Article  CAS  PubMed  Google Scholar 

  71. Hu X, Estecio MR, Chen R, Reuben A, Wang L, Fujimoto J et al (2021) Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas. Nat Commun 12(1):687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Flavahan WA, Gaskell E, Bernstein BE (2017) Epigenetic plasticity and the hallmarks of cancer. Science 357(6348)

    Google Scholar 

  73. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Loukas I, Simeoni F, Milan M, Inglese P, Patel H, Goldstone R, et al (2022) Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia. Cancer Cell

    Google Scholar 

  75. Akbari V, Garant JM, O’Neill K, Pandoh P, Moore R, Marra MA et al (2021) Megabase-scale methylation phasing using nanopore long reads and NanoMethPhase. Genome Biol 22(1):68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Weigel D, Colot V (2012) Epialleles in plant evolution. Genome Biol 13(10):249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cubas P, Vincent C, Coen E (1999) An epigenetic mutation responsible for natural variation in floral symmetry. Nature 401(6749):157–161

    Article  CAS  PubMed  Google Scholar 

  78. Landan G, Cohen NM, Mukamel Z, Bar A, Molchadsky A, Brosh R et al (2012) Epigenetic polymorphism and the stochastic formation of differentially methylated regions in normal and cancerous tissues. Nat Genet 44(11):1207–1214

    Article  CAS  PubMed  Google Scholar 

  79. Cancer Genome Atlas N (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70

    Google Scholar 

  80. Figueroa ME, Lugthart S, Li Y, Erpelinck-Verschueren C, Deng X, Christos PJ et al (2010) DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 17(1):13–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hansen KD, Timp W, Bravo HC, Sabunciyan S, Langmead B, McDonald OG et al (2011) Increased methylation variation in epigenetic domains across cancer types. Nat Genet 43(8):768–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Mazor T, Pankov A, Johnson BE, Hong C, Hamilton EG, Bell RJA et al (2015) DNA methylation and somatic mutations converge on the cell cycle and define similar evolutionary histories in brain tumors. Cancer Cell 28(3):307–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW et al (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A 89(5):1827–1831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Casado-Pelaez M, Bueno-Costa A, Esteller M (2022) Single cell cancer epigenetics. Trends Cancer. 8(10):820–838

    Article  CAS  PubMed  Google Scholar 

  85. Ahmed YW, Alemu BA, Bekele SA, Gizaw ST, Zerihun MF, Wabalo EK et al (2022) Epigenetic tumor heterogeneity in the era of single-cell profiling with nanopore sequencing. Clin Epigenetics 14(1):107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Euskirchen P, Bielle F, Labreche K, Kloosterman WP, Rosenberg S, Daniau M et al (2017) Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing. Acta Neuropathol 134(5):691–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Varley KE, Mutch DG, Edmonston TB, Goodfellow PJ, Mitra RD (2009) Intra-tumor heterogeneity of MLH1 promoter methylation revealed by deep single molecule bisulfite sequencing. Nucleic Acids Res 37(14):4603–4612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E et al (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483(7390):479–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Xie H, Wang M, de Andrade A, Bonaldo Mde F, Galat V, Arndt K et al (2011) Genome-wide quantitative assessment of variation in DNA methylation patterns. Nucleic Acids Res 39(10):4099–4108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Oakes CC, Claus R, Gu L, Assenov Y, Hullein J, Zucknick M et al (2014) Evolution of DNA methylation is linked to genetic aberrations in chronic lymphocytic leukemia. Cancer Discov 4(3):348–361

    Article  CAS  PubMed  Google Scholar 

  91. Shibata D (2011) Mutation and epigenetic molecular clocks in cancer. Carcinogenesis 32(2):123–128

    Article  CAS  PubMed  Google Scholar 

  92. Bachman M, Uribe-Lewis S, Yang X, Williams M, Murrell A, Balasubramanian S (2014) 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem 6(12):1049–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rampal R, Alkalin A, Madzo J, Vasanthakumar A, Pronier E, Patel J et al (2014) DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep 9(5):1841–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Sardina JL, Collombet S, Tian TV, Gomez A, Di Stefano B, Berenguer C, et al (2018) Transcription factors drive Tet2-mediated enhancer demethylation to reprogram cell fate. Cell Stem Cell 23(5):727–741 7e9

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sheng Li .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Li, S. (2023). Inferring the Cancer Cellular Epigenome Heterogeneity via DNA Methylation Patterns. In: Chen, J., Wang, G.G., Lu, J. (eds) Epigenetics in Oncology . Cancer Treatment and Research, vol 190. Springer, Cham. https://doi.org/10.1007/978-3-031-45654-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-45654-1_12

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-45653-4

  • Online ISBN: 978-3-031-45654-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics