Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression

Lindsay M. Lafave, Rachel E. Savage, Jason D. Buenrostro

Research output: Contribution to journalReview articlepeer-review

Abstract

Cancer initiation is driven by the cooperation between genetic and epigenetic aberrations that disrupt gene regulatory programs critical to maintaining specialized cellular functions. After initiation, cells acquire additional genetic and epigenetic alterations influenced by tumor-intrinsic and -extrinsic mechanisms, which increase intratumoral heterogeneity, reshape the cell's underlying gene regulatory networks and promote cancer evolution. Furthermore, environmental or therapeutic insults drive the selection of heterogeneous cell states, with implications for cancer initiation, maintenance, and drug resistance. The advancement of single-cell genomics has begun to uncover the full repertoire of chromatin and gene expression states (cell states) that exist within individual tumors. These single-cell analyses suggest that cells diversify in their regulatory states upon transformation by co-opting damage-induced and nonlineage regulatory programs that can lead to epigenomic plasticity. Here, we review these recent studies related to regulatory state changes in cancer progression and highlight the growing single-cell epigenomics toolkit poised to address unresolved questions in the field.

Original languageEnglish (US)
Pages (from-to)167-185
Number of pages19
JournalAnnual Review of Cancer Biology
Volume6
DOIs
StatePublished - Apr 2022

Keywords

  • cancer evolution
  • DNA methylation
  • drug resistance
  • lineage infidelity
  • plasticity
  • single-cell epigenomics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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