Mutational Profiling of Non-Small Cell Lung Cancer (NSCLC) by Sequenom's OncoCarta™ Panel
DM Kohler, T John, M Tsao. University Health Network and Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada
Background: Large scale genomic sequencing of lung adenocarcinomas have recently revealed the frequent occurrence of mutations within a large number of genes known to play an important role in carcinogenesis. These include oncogenes, growth factor receptors, signal transduction and tumor suppressor genes. The presence of mutation in some of these genes (e.g. KRAS and EGFR) has been correlated with sensitivity or resistance to chemotherapy and/or novel targeted therapies. In the near future, the management of lung cancer patients will require knowledge of the full mutation spectrum of the tumor; as this will play an important role in guiding treatment decisions.
Design: The goal of this study was to explore the feasibility of high throughput profiling of potential mutations in formalin-fixed and paraffin embedded primary NSCLC samples. Using the HE slide as a guide, high tumor cellularity areas of the tumor paraffin blocks were sampled using the 1 mm coring needle of tissue microarrayer. The isolated DNA was analysed by the Oncocarta™ panel (Sequenom®, San Diego, CA), which has the potential to identify 238 mutations across 19 oncogenes using PCR with detection by mass spectrometry.
Results: Altogether, 100 cases of resected NSCLC were studied. Mutations were detected in 38 (38%) cases, including 32 (59%) of adenocarcinoma and 6 (30%) of squamous cell carcinoma. The mutations detected included the those on EGFR tyrosine kinase domain, KRAS, and PI3KCA. Consistent with previous reports, KRAS and EGFR mutations were found mainly in adenocarcinoma (30% and 20%, respectively), while PI3KCA mutations were found mainly in squamous cell carcinomas.
Conclusions: Mutational profiling of routine clinical lung cancer samples is feasible for identification of critical genetic aberrations in NSCLC.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 258, Tuesday Morning