geneOmbio technologies has been working on development and offering various oncology related tests having prognostic value as well as pharmacogenetic significance. Recently we have worked on development of an important test for Breast cancer. Breast cancer is the most common cancer in women globally. Approximately 1.7 million new cases were reported in 2012 and around 8.2 million breast cancer related deaths occurred worldwide in the same year (Cancer Research UK). A 5% – 10% of breast cancer cases are hereditary which result due to abnormalities in two genes BRCA1 and BRCA2. Most other cases of breast cancer result due to somatic mutation taking place in certain breast cells and these genetic changes are acquired during a person’s lifetime. One such gene that will be a focus of this study is PIK3CA.

PI3K Pathway: Phosphatidylinositol-3-kinase (PI3K) is one of the major signaling pathways which plays a crucial role in cell processes like growth, proliferation, metabolism, motility, differentiation and apoptosis (Samuels et al., 2004, Karakas et al., 2006). PI3Ks possess oncogenic properties and genetic alteration in several elements of this pathway results in formation of cancer. Activation of PI3K pathway as a result of somatic mutation in its catalytic subunit p110α encoded by PIK3CA is responsible for different human cancers (Li et al., 2006). According to the COSMIC database (Catalogue of Somatic Mutations in Cancer Database) PIK3CA mutations in exon 9 and exon 20 have been described in 25% – 40% of breast cancers (Harle et al., 2012). The four hotspot PIK3CA mutations that are most common in breast cancer are E542K, E545K in exon 9 and H1047R, H1047L in exon 20. Furthermore, as mutations in PIK3CA are linked with activation of PI3K/AKT pathway, they also play a major role in therapeutic and prognosis schemes. With the development of new drugs targeting PI3K pathway, it will be increasingly important to identify mutations in PIK3CA gene. Direct sequencing is the most common technique used for scanning the mutations but has low sensitivity (15% – 25%), it detects mutations only when sufficient mutant DNA is present. Hence it can be time consuming and complex.

Several alternative assays with improved sensitivity have been developed over the time which include real-time PCR, amplification refractory mutation system (PCR-ARMS), high resolution melting assay (PCR-HRM), pyrosequencing, Snapshot genotyping, multiplex PCR-mass spectroscopy and many others (Ang et al., 2013). ARMS PCR is a powerful real time PCR based technique which combines ARMS and bi-functional fluorescent primer/probe molecule (Scorpion) for targeting specific mutations. Primers are designed against the specific mutations and an amplicon is produced only when the mutation is present in the sample. At geneOmbio, we have also developed ARMS PCR method for detection of PIK3CA mutations.

Clinical significance – PIK3CA mutation has been associated with poor prognosis in endometrial, breast and colorectal cancers. Mutations in exons 9 and 20 of PIK3CA have also been associated with resistance to cetuximab therapy in patients with colorectal cancer. Acceptable specimens include formalin-fixed, paraffin-embedded tissue blocks or slides with at least 5% tumor present, though at least 20% is preferred.

geneOmbio Technologies has seen lot of success in terms of division wise business achievement in past ten months. We wish this will continue further in next financial year. Team GBL would be focusing on development of newer business segment and tie up with more clients in days to come. In January 2017, we completed one of the most prestigious toxicogenomics project from renowned CRO. Our aim is to gain more such projects that would make brand geneOmbio one of the leading player in subcontracting projects domain across country.

– Yashwant Chavan

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