title: Biomarkers of genome instability and cancer epigenetics.
abstract: Tumorigenesis is a multistep process involving genetic and epigenetic alterations that drive somatic evolution from normal human cells to malignant derivatives. Collectively, genetic and epigenetic alterations might be combined into biomarkers for the assessment of risk, the detection of early stage tumors, and accurate tumor characterization before and after treatment. Recent efforts have provided systematic approaches to cancer genomics through the application of massive sequencing of specific tumor types. Here, we review biomarkers of genome instability and epigenetics. Cancer evolvability and adaptation emerge through genetic and epigenetic lesions of a variety of sizes and qualities-from point mutations and small insertions/deletions to large-scale chromosomal rearrangements, alterations in whole chromosome copy number, preferential allelic expression of cancer risk alleles, and mechanisms that increase tumor mutation rates. We also review specific epigenetic mechanisms that facilitate or hinder tumor adaptation, including DNA methylation, histone modification, nucleosome remodeling, transcription factor activity, and small non-coding RNAs. Given the complexity of the carcinogenic process, the challenge ahead will be to interpret disparate signals across hundreds of genes and summarize these signals into a single actionable diagnosis that translates into specific treatments. Another challenge is to refine preventive efforts through the identification of epigenetic processes that mediate increased cancer rates in individuals exposed to sources of toxic environmental stress and pollution, specially through development and early childhood.
authors.affiliation: Genetics Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.
authors.forename: Adriana H O
authors.initials: AH
authors.lastname: Reis
authors.affiliation: Genetics Program, Instituto Nacional de Cancer, Rio de Janeiro, Brazil.|Genetics and Molecular Biology Department, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.|Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Vargas
authors.affiliation: Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T. H. Chan School of Public Health, 665 Huntington Avenue, Bldg 2, Rm 219, Boston, MA, 02115, USA. blemos@hsph.harvard.edu.
authors.forename: Bernardo
authors.identifier: http://orcid.org/0000-0001-6996-9483
authors.initials: B
authors.lastname: Lemos
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Epigenetics; Genome instability; Tumorigenesis