Extensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumours, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explainable by the evolutionary ecology of organs' theory, in the same way that environmental adversity shapes mutation rates and level of polymorphism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at suppressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis. Lay summary: Different levels of mutations and intra-tumour heterogeneity have been observed between cancer types and organs. Anti-cancer defences are unequal between our organs. We propose that mostly aggressive neoplasms (i.e. higher mutational and ITH levels), succeed in emerging and developing in organs with strong defences.

中文翻译：

---

器官之间突变过程和肿瘤内异质性的差异：局部选择性过滤假说。

肿瘤内部和肿瘤之间存在广泛的多样性（遗传、细胞遗传学、表观遗传和表型），但目前对这些变异背后的原因以及器官之间一致的分层模式知之甚少。我们认为，这些现象至少可以部分地用器官进化生态学理论来解释，就像环境逆境影响生物体的突变率和多态性水平一样。生物体中的器官可以被视为专门的生态系统，出于生态和进化的原因，它们在抑制肿瘤方面或多或少有效。当对肿瘤施加强大选择压力的器官中确实出现恶性肿瘤时，其组成细胞预计会表现出多种可能的生存策略，从依赖赌注对冲的超突变表型到持续存在（高突变率和高多样性），一些变异性较差的变异体对于自然防御来说是不可见的。相反，当肿瘤抑制较弱时，有利于极端生存策略的选择压力就会放松，因此肿瘤会发生适度的变化。我们对这一假设进行了全面的概述。简单总结：在癌症类型和器官之间观察到不同水平的突变和肿瘤内异质性。我们的器官之间的抗癌防御能力是不平等的。我们认为，大多数侵袭性肿瘤（即较高的突变和 ITH 水平）能够在具有强大防御能力的器官中成功出现和发展。