Single-Cell Epigenomics in Cancer: Charting a Course to Clinical Impact

References

• Meissner A . Epigenetic modifications in pluripotent and differentiated cells. Nature Biotechnol.28(10), 1079–1088 (2010).
   PubMed Web of Science ®Google Scholar
• Baylin SB , JonesPA. A decade of exploring the cancer epigenome - biological and translational implications. Nat. Rev. Cancer11(10), 726–734 (2011).
   PubMed Web of Science ®Google Scholar
• Jones PA . Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet.13(7), 484–492 (2012).
   PubMed Web of Science ®Google Scholar
• Zhao Z , ShilatifardA. Epigenetic modifications of histones in cancer. Genome Biol.20(1), 245 (2019).
   PubMed Web of Science ®Google Scholar
• Biswas S , RaoCM. Epigenetic tools (the writers, the readers and the erasers) and their implications in cancer therapy. Eur. J. Pharmacol.837, 8–24 (2018).
   PubMed Web of Science ®Google Scholar
• Schubeler D . Function and information content of DNA methylation. Nature517(7534), 321–326 (2015).
   PubMed Web of Science ®Google Scholar
• Okano M , XieS , LiE. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet.19(3), 219–220 (1998).
   PubMed Web of Science ®Google Scholar
• Wu H , ZhangY. Reversing DNA methylation: mechanisms, genomics and biological functions. Cell156(1-2), 45–68 (2014).
   PubMed Web of Science ®Google Scholar
• Feng Q , ZhangY. The MeCP1 complex represses transcription through preferential binding, remodeling and deacetylating methylated nucleosomes. Genes Dev.15(7), 827–832 (2001).
   PubMed Web of Science ®Google Scholar
• Leighton G , WilliamsDC. The methyl-CpG–binding domain 2 and 3 proteins and formation of the nucleosome remodeling and deacetylase complex. J. Mol. Biol.432(6), 1624–1639 (2019).
   PubMed Web of Science ®Google Scholar
• Itzen F , GreifenbergAK , BöskenCA , GeyerM. Brd4 activates P-TEFb for RNA polymerase II CTD phosphorylation. Nucleic Acids Res.42(12), 7577–7590 (2014).
   PubMed Web of Science ®Google Scholar
• Jones PA , IssaJP , BaylinS. Targeting the cancer epigenome for therapy. Nat. Rev. Genet.17(10), 630–641 (2016).
   PubMed Web of Science ®Google Scholar
• Du Q , BertSA , ArmstrongNJet al. Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer. Nat. Commun.10(1), 416 (2019).
   PubMedGoogle Scholar
• Thienpont B , SteinbacherJ , ZhaoHet al. tumor hypoxia causes DNA hypermethylation by reducing TET activity. Nature537(7618), 63–68 (2016).
   PubMed Web of Science ®Google Scholar
• Ng JM , YuJ. Promoter hypermethylation of tumor suppressor genes as potential biomarkers in colorectal cancer. Int. J. Mol. Sci.16(2), 2472–2496 (2015).
   PubMed Web of Science ®Google Scholar
• Bhatia V , GoelMM , MakkerAet al. Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma. Biomed. Res. Int.2014, 248419–248419 (2014).
   PubMed Web of Science ®Google Scholar
• Liyanage C , WathupolaA , MuraleetharanS , PereraK , PunyadeeraC , UdagamaP. Promoter hypermethylation of tumor-suppressor genes p16(INK4a), RASSF1A, TIMP3 and PCQAP/MED15 in salivary DNA as a quadruple biomarker panel for early detection of oral and oropharyngeal cancers. Biomolecules9(4), 148 (2019).
   PubMed Web of Science ®Google Scholar
• Lv X , YeG , ZhangX , HuangT. p16 Methylation was associated with the development, age, hepatic viruses infection of hepatocellular carcinoma and p16 expression had a poor survival: a systematic meta-analysis (PRISMA). Medicine96(38), e8106 (2017).
   PubMed Web of Science ®Google Scholar
• Liu Y , LanQ , SiegfriedJM , LuketichJD , KeohavongP. Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia8(1), 46–51 (2006).
   PubMed Web of Science ®Google Scholar
• Bilgrami SM , QureshiSA , PervezS , AbbasF. Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer. Springerplus3, 178 (2014).
   PubMedGoogle Scholar
• Fiolka R , ZuborP , JanusicovaVet al. Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer. Oncol. Rep.30(6), 2878–2886 (2013).
   PubMed Web of Science ®Google Scholar
• Kang JH , KimSJ , NohDYet al. Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma. Lab. Invest.81(4), 573–579 (2001).
   PubMed Web of Science ®Google Scholar
• Zhang L , LongX. Association of BRCA1 promoter methylation with sporadic breast cancers: evidence from 40 studies. Sci. Rep.5, 17869–17869 (2015).
   PubMed Web of Science ®Google Scholar
• Kondo Y , ShenL , IssaJP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol. Cell. Biol.23(1), 206–215 (2003).
   PubMed Web of Science ®Google Scholar
• Di Cerbo V , SchneiderR. Cancers with wrong HATs: the impact of acetylation. Brief Funct. Genomics12(3), 231–243 (2013).
   PubMed Web of Science ®Google Scholar
• Glozak MA , SetoE. Histone deacetylases and cancer. Oncogene26(37), 5420–5432 (2007).
   PubMed Web of Science ®Google Scholar
• Kandoth C , MclellanMD , VandinFet al. Mutational landscape and significance across 12 major cancer types. Nature502(7471), 333–339 (2013).
   PubMed Web of Science ®Google Scholar
• Shlush LI , ZandiS , MitchellAet al. Identification of pre-leukaemic haematopoietic stem cells in acute leukemia. Nature506(7488), 328–333 (2014).
   PubMed Web of Science ®Google Scholar
• Jan M , SnyderTM , Corces-ZimmermanMRet al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci. Transl. Med.4, 149ra118 (2012).
   PubMed Web of Science ®Google Scholar
• Abelson S , CollordG , NgSWKet al. Prediction of acute myeloid leukemia risk in healthy individuals. Nature559(7714), 400–404 (2018).
   PubMed Web of Science ®Google Scholar
• Desai P , Mencia-TrinchantN , SavenkovOet al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat. Med.24(7), 1015–1023 (2018).
   PubMed Web of Science ®Google Scholar
• The Cancer Genome Atlas Research Network . Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med.368(22), 2059–2074 (2013).
   PubMed Web of Science ®Google Scholar
• Spencer DH , Russler-GermainDA , KetkarSet al. CpG island hypermethylation mediated by DNMT3A is a consequence of AML progression. Cell168(5), 801–816e813 (2017).
   PubMed Web of Science ®Google Scholar
• Rasmussen KD , JiaG , JohansenJVet al. Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev.29(9), 910–922 (2015).
   PubMed Web of Science ®Google Scholar
• Brocks D , AssenovY , MinnerSet al. Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Rep.8(3), 798–806 (2014).
   PubMed Web of Science ®Google Scholar
• Li S , Garrett-BakelmanFE , ChungSSet al. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat. Med.22(7), 792–799 (2016).
   PubMed Web of Science ®Google Scholar
• Pan H , JiangY , BoiMet al. Epigenomic evolution in diffuse large B-cell lymphomas. Nat. Commun.6, 6921 (2015).
   PubMed Web of Science ®Google Scholar
• Gaiti F , ChaligneR , GuHet al. Epigenetic evolution and lineage histories of chronic lymphocytic leukemia. Nature569(7757), 576–580 (2019).
   PubMed Web of Science ®Google Scholar
• Bian S , HouY , ZhouXet al. Single-cell multiomics sequencing and analyses of human colorectal cancer. Science362(6418), 1060–1063 (2018).
   PubMed Web of Science ®Google Scholar
• Song L , LiY. Progress on the clinical application of the SEPT9 gene methylation assay in the past 5 years. Biomark. Med.11(6), 415–418 (2017).
   PubMed Web of Science ®Google Scholar
• Chan KCA , JiangP , ChanCWMet al. Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc. Natl Acad. Sci. USA110(47), 18761–18768 (2013).
   PubMed Web of Science ®Google Scholar
• Shen SY , SinghaniaR , FehringerGet al. Sensitive tumor detection and classification using plasma cell-free DNA methylomes. Nature563(7732), 579–583 (2018).
   PubMed Web of Science ®Google Scholar
• Pixberg CF , RabaK , MullerFet al. Analysis of DNA methylation in single circulating tumor cells. Oncogene363223–3231 (2017).
   PubMed Web of Science ®Google Scholar
• Pixberg CF , SchulzWA , StoeckleinNH , NevesRPL. Characterization of DNA methylation in circulating tumor cells. Genes6(4), 1053–1075 (2015).
   PubMed Web of Science ®Google Scholar
• Stirzaker C , ZotenkoE , SongJZet al. Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value. Nat. Commun.6, 5899 (2015).
   PubMed Web of Science ®Google Scholar
• Moran S , Martínez-CardúsA , SayolsSet al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol.17(10), 1386–1395 (2016).
   PubMed Web of Science ®Google Scholar
• Wick W , WellerM , VanDen Bent Met al. MGMT testing – the challenges for biomarker-based glioma treatment. Nat. Rev. Neurol.10, 372 (2014).
   PubMed Web of Science ®Google Scholar
• Cheng Y , HeC , WangMet al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct. Target. Ther.4(1), 62 (2019).
   PubMedGoogle Scholar
• Fenaux P , MuftiGJ , Hellstrom-LindbergEet al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J. Clin. Oncol.28(4), 562–569 (2010).
   PubMed Web of Science ®Google Scholar
• Fennell KA , BellCC , DawsonMA. Epigenetic therapies in acute myeloid leukemia: where to from here?Blood134(22), 1891–1901 (2019).
   PubMed Web of Science ®Google Scholar
• Alqahtani A , ChoucairK , AshrafMet al. Bromodomain and extra-terminal motif inhibitors: a review of preclinical and clinical advances in cancer therapy. Future Sci. OA5(3), Fso372 (2019).
   PubMed Web of Science ®Google Scholar
• Mohammad HP , BarbashO , CreasyCL. Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer. Nat. Med.25(3), 403–418 (2019).
   PubMed Web of Science ®Google Scholar
• Jones PA , OhtaniH , ChakravarthyA , DeCarvalho DD. Epigenetic therapy in immune-oncology. Nat. Rev. Cancer19(3), 151–161 (2019).
   PubMed Web of Science ®Google Scholar
• Clark SJ , LeeHJ , SmallwoodSA , KelseyG , ReikW. Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity. Genome Biol.17, 72 (2016).
   PubMed Web of Science ®Google Scholar
• Kelsey G , StegleO , ReikW. Single-cell epigenomics: recording the past and predicting the future. Science358(6359), 69–75 (2017).
   PubMed Web of Science ®Google Scholar
• Schwartzman O , TanayA. Single-cell epigenomics: techniques and emerging applications. Nat. Rev. Genet.16, 716 (2015).
   PubMed Web of Science ®Google Scholar
• Knapp DJHF , HammondCA , HuiTet al. Single-cell analysis identifies a CD33+ subset of human cord blood cells with high regenerative potential. Nat. Cell Biol.20(6), 710–720 (2018).
   PubMed Web of Science ®Google Scholar
• Angermueller C , ClarkSJ , LeeHJet al. Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity. Nat. Methods13(3), 229–232 (2016).
   PubMed Web of Science ®Google Scholar
• Argelaguet R , ClarkSJ , MohammedHet al. Multi-omics profiling of mouse gastrulation at single-cell resolution. Nature576(7787), 487–491 (2019).
   PubMed Web of Science ®Google Scholar
• Lareau CA , DuarteFM , ChewJGet al. Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility. Nature Biotechnol.37(8), 916–924 (2019).
   PubMed Web of Science ®Google Scholar
• Zhu C , PreisslS , RenB. Single-cell multimodal omics: the power of many. Nature methods17(1), 11–14 (2020).
   PubMed Web of Science ®Google Scholar
• Satpathy AT , GranjaJM , YostKEet al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nature Biotechnol.37(8), 925–936 (2019).
   PubMed Web of Science ®Google Scholar
• Hemberger M , DeanW , ReikW. Epigenetic dynamics of stem cells and cell lineage commitment. Digging Waddington’s canal. Nat. Rev. Mol. Cell Biol.10, 526–537 (2009).
   PubMed Web of Science ®Google Scholar
• Lee HJ , HoreTA , ReikW. Reprogramming the methylome: erasing memory and creating diversity. Cell Stem Cell14(6), 710–719 (2014).
   PubMed Web of Science ®Google Scholar
• Giraldo NA , Sanchez-SalasR , PeskeJDet al. The clinical role of the TME in solid cancer. Br. J. Cancer120(1), 45–53 (2019).
   PubMed Web of Science ®Google Scholar
• Gustavson MD , Bourke-MartinB , ReillyDet al. Standardization of HER2 immunohistochemistry in breast cancer by automated quantitative analysis. Arch. Pathol. Lab. Med.133(9), 1413–1419 (2009).
   PubMed Web of Science ®Google Scholar
• Suvà ML , TiroshI. Single-cell RNA sequencing in cancer: lessons learned and emerging challenges. Mol. Cell75(1), 7–12 (2019).
   PubMed Web of Science ®Google Scholar
• Gao R , DavisA , McdonaldTOet al. Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat. Genet.48(10), 1119–1130 (2016).
   PubMed Web of Science ®Google Scholar
• Tirosh I , VenteicherAS , HebertCet al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature539(7628), 309–313 (2016).
   PubMed Web of Science ®Google Scholar
• Van Galen P , HovestadtV , WadsworthIi MHet al. Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity. Cell176(6), 1265–1281.e1224 (2019).
   PubMed Web of Science ®Google Scholar
• Buenrostro JD , WuB , LitzenburgerUMet al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature523(7561), 486–490 (2015).
   PubMed Web of Science ®Google Scholar
• Farlik M , SheffieldNC , NuzzoA , DatlingerP , SchöneggerA , KlughammerJ. Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep.10(8), 1386–1397 (2015).
   PubMed Web of Science ®Google Scholar
• Litzenburger UM , BuenrostroJD , WuBet al. Single-cell epigenomic variability reveals functional cancer heterogeneity. Genome Biol.18(1), 15 (2017).
   PubMedGoogle Scholar
• Corces MR , BuenrostroJD , WuBet al. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution. Nat. Genet.48(10), 1193–1203 (2016).
   PubMed Web of Science ®Google Scholar
• American Cancer Society . Cancer facts & figures 2020. (2020). www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf
   Google Scholar
• Lambert AW , PattabiramanDR , WeinbergRA. Emerging biological principles of metastasis. Cell168(4), 670–691 (2017).
   PubMed Web of Science ®Google Scholar
• Fares J , FaresMY , KhachfeHH , SalhabHA , FaresY. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct. Target. Ther.5(1), 28 (2020).
   PubMed Web of Science ®Google Scholar
• Chatterjee A , RodgerEJ , EcclesMR. Epigenetic drivers of tumorigenesis and cancer metastasis. Semin. Cancer Biol.51, 149–159 (2018).
   PubMed Web of Science ®Google Scholar
• Tam WL , WeinbergRA. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med.19, 1438 (2013).
   PubMed Web of Science ®Google Scholar
• Chaffer Christine l , MarjanovicNemanja d , LeeTet al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell154(1), 61–74 (2013).
   PubMed Web of Science ®Google Scholar
• Ramskold D , LuoS , WangY-Cet al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat. Biotech.30(8), 777–782 (2012).
   PubMed Web of Science ®Google Scholar
• Pastushenko I , BrisebarreA , SifrimAet al. Identification of the tumor transition states occurring during EMT. Nature556(7702), 463–468 (2018).
   PubMed Web of Science ®Google Scholar
• Ting David t , WittnerBen s , LigorioMet al. Single-Cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep.8(6), 1905–1918 (2014).
   PubMed Web of Science ®Google Scholar
• Miyamoto DT , ZhengY , WittnerBSet al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science349(6254), 1351–1356 (2015).
   PubMed Web of Science ®Google Scholar
• Lawson DA , BhaktaNR , KessenbrockK , PrummelKD , YuY , TakaiK. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature526 (2015).
   Google Scholar
• Gkountela S , Castro-GinerF , SzczerbaBMet al. Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding. Cell176(1), 98–112.e114 (2019).
   PubMed Web of Science ®Google Scholar
• Iorgulescu JB , HararyM , ZoggCKet al. Improved risk-adjusted survival for melanoma brain metastases in the era of checkpoint blockade immunotherapies: results from a national cohort. Cancer Immunol. Res.6(9), 1039–1045 (2018).
   PubMed Web of Science ®Google Scholar
• Sambi M , BagheriL , SzewczukMR. Current challenges in cancer immunotherapy: multimodal approaches to improve efficacy and patient response rates. J. Oncol.2019, 4508794 (2019).
   PubMed Web of Science ®Google Scholar
• Jerby-Arnon L , ShahP , CuocoMSet al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell175(4), 984–997.e924 (2018).
   PubMed Web of Science ®Google Scholar
• Duchmann M , ItzyksonR. Clinical update on hypomethylating agents. Int. J. Hematol.110(2), 161–169 (2019).
   PubMed Web of Science ®Google Scholar
• Kim D , KobayashiT , VoisinBet al. Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report. Nat. Med.26(2), 236–243 (2020).
   PubMed Web of Science ®Google Scholar
• Flores-Montero J , Sanoja-FloresL , PaivaBet al. Next generation flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia31(10), 2094–2103 (2017).
   PubMed Web of Science ®Google Scholar
• Theunissen P , MejstrikovaE , SedekLet al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood129(3), 347–357 (2017).
   PubMed Web of Science ®Google Scholar
• Ossenkoppele G , SchuurhuisGJ. MRD in AML: does it already guide therapy decision-making?Hematology2016(1), 356–365 (2016).
   PubMedGoogle Scholar
• Izevbaye I , LiangLY , MatherC , El-HallaniS , MaglantayRJr , SainiL. Clinical validation of a myeloid next-generations sequencing panel for single-nucleotide variants, insertions/deletions and fusion genes. J. Mol. Diagn.22(2), 208–219 (2020).
   PubMed Web of Science ®Google Scholar
• Sabour L , SabourM , GhorbianS. Clinical applications of next-generation sequencing in cancer diagnosis. Pathol. Oncol. Res.23(2), 225–234 (2017).
   PubMed Web of Science ®Google Scholar
• Kim T , MoonJH , AhnJ-Set al. Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse. Blood132(15), 1604–1613 (2018).
   PubMed Web of Science ®Google Scholar
• Jongen-Lavrencic M , GrobT , HanekampDet al. Molecular minimal residual disease in acute myeloid leukemia. N. Engl. J. Med.378(13), 1189–1199 (2018).
   PubMed Web of Science ®Google Scholar
• Enjeti AK , ChapmanK , TaylorPJ , MeldrumC. Congenital late onset thrombotic thrombocytopenic purpura: a diagnostic challenge. Pathology47(6), 585–586 (2015).
   PubMed Web of Science ®Google Scholar
• Salomon R , KaczorowskiD , Valdes-MoraFet al. Droplet-based single cell RNAseq tools: a practical guide. Lab Chip19(10), 1706–1727 (2019).
   PubMed Web of Science ®Google Scholar