A continuum model for tumour suppression

摘要

This year, 2011, marks the forty-year anniversary of the statistical analysis of retinoblastoma that provided the first evidence that tumorigenesis can be initiated by as few as two mutations. This work provided the foundation for the two-hit hypothesis that explained the role of recessive tumour suppressor genes (TSGsJ in dominantly inherited cancer susceptibility syndromes. However, four decades later, it is now known that even partial inactivation of tumour suppressors can critically contribute to tumorigenesis. Here we analyse this evidence and propose a continuum model of TSG function to explain the full range of TSG mutations found in cancer.%最初由A_fred Knudsorl以眼癌作为 个模型于rn1971年提出的关于肿瘤发生的“two-hit"假rn说，解释了隐性“肿瘤抑制基因”(TSGs)在绝rn大部分为遗传性的癌症易感性综合症中的作rn用；在这些综合症中，肿瘤发生后来被发现需rn要两个突变，一个肿瘤抑制基因的每个版本中rn各个。40年之后，人们已经清楚，即便是肿rn瘤抑制因子的部分失活也会对肿瘤发生做出关rn键性的贡献。由Alice Berger、Aifred Knudson rn和Pier Paolo Pandolfi撰写的这篇Review文章，rn提出了一个关于TSG功能的连续模型，来解释rn在癌症中所发现的所有TSG突变。