Understanding why driver mutations that promote cancer are sometimes rare is important for precision medicine since it would help in their identification. Driver mutations are largely discovered through their frequencies. Thus, rare mutations often escape detection. Unlike high-frequency drivers, low-frequency drivers can be tissue specific; rare drivers have extremely low frequencies. Here, we discuss rare drivers and strategies to discover them. We suggest that allosteric driver mutations shift the protein ensemble from the inactive to the active state. Rare allosteric drivers are statistically rare since, to switch the protein functional state, they cooperate with additional mutations, and these are not considered in the patient cancer-specific protein sequence analysis. A complete landscape of mutations that drive cancer will reveal tumor-specific therapeutic vulnerabilities.

中文翻译：

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为什么某些驾驶员突变很少发生？

对于精密医学来说，了解为什么有时很少会引起癌症的驱动基因突变非常重要，因为这将有助于他们的识别。驾驶员突变主要是通过其频率发现的。因此，罕见的突变通常无法被检测到。与高频驱动器不同，低频驱动器可以针对组织。罕见的驱动器具有极低的频率。在这里，我们讨论了罕见的驱动因素和发现它们的策略。我们建议变构驱动程序突变将蛋白质集合从非活动状态转变为活动状态。稀有的变构驱动子在统计上是罕见的，因为要切换蛋白质功能状态，它们会与其他突变协同作用，并且在患者癌症特异性蛋白质序列分析中未考虑这些突变。