The three RAS genes — HRAS, NRAS and KRAS — are collectively mutated in one-third of human cancers, where they act as prototypic oncogenes. Interestingly, there are rather distinct patterns to RAS mutations; the isoform mutated as well as the position and type of substitution vary between different cancers. As RAS genes are among the earliest, if not the first, genes mutated in a variety of cancers, understanding how these mutation patterns arise could inform on not only how cancer begins but also the factors influencing this event, which has implications for cancer prevention. To this end, we suggest that there is a narrow window or ‘sweet spot’ by which oncogenic RAS signalling can promote tumour initiation in normal cells. As a consequence, RAS mutation patterns in each normal cell are a product of the specific RAS isoform mutated, as well as the position of the mutation and type of substitution to achieve an ideal level of signalling.

三种RAS基因-HRAS，NRAS和KRAS-在三分之一的人类癌症中被集体突变，在癌症中它们充当原型致癌基因。有趣的是，RAS突变存在截然不同的模式。不同癌症之间突变的同工型以及取代的位置和类型各不相同。由于RAS基因是最早（即使不是最早）在多种癌症中突变的基因之一，因此了解这些突变方式如何产生不仅可以告知癌症的发生方式，而且可以影响影响该事件的因素，这对癌症的预防具有重要意义。为此，我们建议存在一个狭窄的窗口或“最佳点”，致癌RAS信号可通过该窗口或“甜点”促进正常细胞中的肿瘤起始。结果，每个正常细胞中的RAS突变模式是特定RAS同种型突变的产物，