Edit ID | Edit Comment | Time | |
---|
402821 | New Interpretation | 01/22/2019 1:41 PM |
Before
The interpretation was not yet created, or had been deleted.After (Current Version)
Tier 2InterpretationThe catalytic subunit of phosphatidylinositol-3-kinase (PI3K) is encoded by the PIK3CA gene. PIK3CA is among the most commonly mutated genes in cancer and aberrant activation of PI3K is a transforming event. PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways. The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with three hotspots (E542K, E545K, and H1047R/L). PIK3CA mutations have been reported in various tumor types including up to 36% and 11% of hepatocellular carcinoma and gastric cancer, respectively. They are detected less frequently in cholangiocarcinoma (~6%) and pancreatic adenocarcinoma (~4%). The predictive and prognostic significance of PIK3CA mutations is unclear and needs further elucidation. Clinical trials targeting PI3K/Akt/mTor pathway inhibitors are available for patients with PIK3CA mutated tumors. The PIK3CA N1044K mutation is known to be oncogenic.
|
Citations- Gymnopoulos M, Elsliger MA, Vogt PK. Rare cancer-specific mutations in PIK3CA show gain of function. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5569-74.
- Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer. 2005 Dec;5 (12):921-9.
- Chandarlapaty S. Negative feedback and adaptive resistance to the targeted therapy of cancer. Cancer Discov. 2012 Apr;2(4):311-9.
- Karakas B, et al. Mutation of the PIK3CA oncogene in human cancers. Br J Cancer 2006;94(4):455-9
- Lee JW, et al. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 2005;24(8):1477-80
- Velho S, et al. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer 2005;41(11):1649-54
- Jiao Y, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet 2013;45(12):1470-3.
- Witkiewicz AK, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun 2015;6():6744
|
Last updated: 2019-01-22 18:41:27 UTC
|