Histone Modifications in Cancer Biology and Prognosis

摘要: Cancer is a disease of genome sequence alterations as well epigenetic changes. Epigenetics refers in part to the mechanisms by which histones affect various DNA-based processes, such gene regulation. Histones are proteins around DNA wraps itself form chromatin – physiologically relevant human genome. modified extensively posttranslational modifications that alter structure and serve recruit or exclude protein complexes from DNA. Aberrations histone occur frequently cancer including changes their levels distribution at promoters, coding regions, repetitive sequences, other genomic elements. Locus-specific may have adverse effects on expression nearby genes but so far not been shown clinical utility. cells also exhibit global specific modifications, generating an additional layer heterogeneity cellular level tumor tissues. Unlike locus-specific changes, can be used define previously unrecognized subsets patients with distinct outcomes. In general, increased prevalence lower prognostic poorer outcome risk recurrence and/or decreased survival probability. Prognostic utility has demonstrated independently for multiple cancers those prostate, lung, kidney, breast, ovary, pancreas, suggesting fundamental association between modification aggressiveness, regardless tissue origin. Cellular predict response certain chemotherapeutic agents, serving predictive biomarkers could inform decisions choice course therapy. The challenge before us understand how established maintained what mechanistic links behavior.