Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets. In addition to mutation, structural variations and partial copy losses involvingPTENandSTK11showed evidence for having functional relevance. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboringIDH1orVHLmutations, suggesting multiple mechanisms for pathway activation.

中文翻译：

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PI3K / AKT / mTOR通路改变的全癌蛋白基因组图谱

在代表32种主要类型的11,219例人类癌症中检查了涉及PI3K / AKT / mTOR途径的分子变化（包括突变，拷贝数，蛋白质或RNA）。在特定的突变基因中，频率，突变热点残基，计算机模拟预测和功能分析都有助于区分更可能具有功能相关性的遗传变异子集。包括PI3K / AKT / mTOR在内的多种致癌途径汇聚在相似的下游转录靶标上。除突变外，涉及PTEN和STK11的结构变异和部分复制丢失也显示出具有功能相关性的证据。大部分癌症显示出高mTOR通路活性，而没有相关的规范遗传或基因组改变，包括带有IDH1或VHL突变的癌症，