A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
A partir de données portant sur 11 219 échantillons tumoraux humains (32 types de cancer), cette étude analyse les anomalies moléculaires associées à une activation de la voie de signalisation PI3K/AKT/mTOR, puis montre que, pour une proportion non négligeable de cancers, une activité élevée de la voie mTOR n'est associée à aucune anomalie génétique ou génomique connue
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 involving PTEN and STK11 showed 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 harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.