A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations

作者：Zhang Yiqun; Ng Patrick Kwok Shing; Kucherlapati Melanie; Chen Fengju; Liu Yuexin; Tsang Yiu Huen; de Velasco Guillermo; Jeong Kang Jin; Akbani Rehan; Hadjipanayis Angela; Pantazi Angeliki; Bristow Christopher A; Lee Eunjung; Mahadeshwar Harshad S; Tang Jiabin; Zhang Jianhua; Yang Lixing; Seth Sahil; Lee Semin; Ren Xiaojia; Song Xingzhi; Sun Huandong; Seidman Jonathan; Luquette Lovelace J; Xi Ruibin; Chin Lynda; Protopopov Alexei; Westbrook Thomas F; Shelley Carl Simon; Choueiri Toni K

来源：Cancer Cell, 2017, 31(6): 820-+.

DOI：10.1016/j.ccell.2017.04.013

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.

• 出版日期2017-6-12