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PIK3CA mutations in Tunisian patients with metastatic colorectal cancer: Patient stratification for targeted therapies
Background
The PI3K signaling pathway plays a key role in the pathogenesis of many cancer types, including colorectal cancer. The PI3K signaling pathway is deregulated due to the amplification, genetic mutation of PIK3CA gene or one component of the PI3K pathway themselves. Mutations in PIK3CA exons 10 and/or 21 are present in 10-20% of colorectal cancers and are associated with other molecular alterations, including RAS mutations. Tumors harboring mutations in PI3K pathway may be less susceptible to treatment using anti-EGFR antibodies and to other targeted therapies.
Methods
This study enrolled 61 patients with metastatic CRC. PIK3CA mutations detection in exons 10 and 21 was performed using simple PCR followed by Sanger sequencing.
Results
Our results showed mutations in PIK3CA in 24,6% (15/61), among them, thirteen was detected on the exon 10 (E542K or I543N) and two mutations on the exon 21 (G1007W and E1012K). The effect of these mutations on the secondary structure of the mRNA were generated using RNAfold 2.4.17.
Conclusions
These PIK3CA mutations could influence and explain, at least in part, the difference in response observed in treated patients with targeted therapies and should be considered for the selection of patients to avoid toxicity of an inactive drug. Furthermore, the PI3K pathway mutation status should be considered in the choice of PI3K inhibitors, currently under clinical investigations.
Legal entity responsible for the study
The author.
Funding
This work was supported by the Tunisian Ministry of Public Health, the Tunisian Ministry of Higher Education and Scientific Research (LR16IPT05).
Disclosures
All authors have declared no conflicts of interest.
