Feinberg Andrew P, Ohlsson Rolf, Henikoff Steven
Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
Nat Rev Genet. 2006 Jan;7(1):21-33. doi: 10.1038/nrg1748.
Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.
癌症被广泛认为是一组具有明显不同生物学特性的异质性疾病，这些疾病由关键肿瘤抑制基因和癌基因中的一系列克隆选择的基因变化引起。然而，最近的数据表明，癌症具有一个根本的共同基础，即基于由“肿瘤祖细胞基因”介导的干/祖细胞的多克隆表观遗传破坏。此外，肿瘤细胞异质性部分归因于祖细胞中的表观遗传变异，表观遗传可塑性与基因损伤共同驱动肿瘤进展。癌症中表观遗传改变的这一关键早期作用，是除了在肿瘤进展后期可替代基因变异的表观遗传改变之外的。因此，非肿瘤性但表观遗传破坏的干/祖细胞可能是癌症风险评估和化学预防的关键靶点。
