The presence of the PIK3CA mutation and the wild-type KRAS, BRAF, CTNNB1 genes, and the intact PTEN expression in 3 sporadic CMV-PTCs may suggest the possible contribution of the PIK3CA mutation in its tumorigenesis.
• PI3K/AKT/mTOR signalling components appear to be differentially implicated in urothelial tumorigenesis and, with the exception of p85aPI3K, are unrelated to the PIK3CA or AKT1 mutational status.
While oncogenic BRAF contributes to the tumorigenesis of both pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms/carcinomas (IPMN/IPMC), PIK3CA mutations were only detected in IPMN/IPMC.
Our data suggest that PIK3CA mutations contribute to the invasion step from intramucosal carcinoma to invasive carcinoma in colorectal carcinogenesis in FAP and HNPCC patients at a similar extent to that seen in sporadic patients.
Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer.
The results suggest PIK3CAH1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells.
These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.
Taken together, our results demonstrate that a subset of PIK3CAmut promote tumorigenesis and suggest that patients with helical domain mutations may be most sensitive to dual PI3Ki/MEKi treatment.
Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population.
The aim of the study was to investigate the molecular occurrence of KRAS, BRAF and PIK3CA mutations in the colorectal tumorigenesis and to study the association of these events with clinicopathological parameters.
RAS-coupled MAPK and PI3K pathways play a fundamental role in thyroid tumorigenesis, and classical genetic alterations upregulating these pathways are well characterized.
Our results show that BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis.
The PI3K/Akt/mTOR pathway is frequently altered in this poorly characterised carcinoma<sub>.</sub> IGF2 was identified here as a key factor in ASCC oncogenesis, as IGF2 was shown to play a crucial role in the PI3K pathway with frequent (~60%) and mutually exclusive genomic alterations in IGF2, IGF1R, PTEN and PIK3CA genes.
Furthermore, PIK3CA amplification was predominantly detected in tumors with no PTEN alterations, suggesting that mutations of PTEN and PIK3CA are mutually exclusive events in gastric tumorigenesis.
These findings suggest that PIK3CA mutations may be a relatively late event and may function primarily in a supporting/modifying role, and not as a primary driver of oncogenesis.