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PI3K - Gene Mutation Analysis

 The enzyme phosphoinositide 3-kinase (PI3K), product of the PIK3CA gene, plays a key role in the cellular survival pathway, one of two pathways activated by receptor tyrosine kinases such as EGFR. Activating mutations of the PIK3CA gene are common in a variety of cancers, including those of breast (27%) and colorectum (19%). Recent studies suggest that such mutations are associated with resistance to trastuzumab (Herceptin™), cetuximab (Erbitux™), panitumumab (Vectibix™) and potentially lapatinib (Tyverb/Tykerb™).

Source BioScience offers PI3K mutation testing based on two alternative CE-marked technologies, both suitable for archival FFPE tissue samples:

• The DxS PI3K Mutation Test uses real-time PCR to detect the 4 most common activating mutations occurring in exons 9 and 20 of the PIK3CA gene
• Pyrosequencing using an assay developed and validated in-house at Source Bioscience to evaluate a total of 9 mutations found in exons 9 and 20

The results of mutation tests are reported as positive or negative for the presence of a particular mutation, along with additional information about relative frequencies of particular mutations in colorectal and lung tumours.

References:

• Berns et al. (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12:395-402
• Sartore-Bianchi et al. (2009) PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851-7.
• Eichhorn et al. (2008) Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 68:9221.

For further information please contact us at: Pharma