Abstract
Introduction:
Comprehensive genomic profiling (CGP) is a molecular diagnostic tool with increasing use in cancer research and treatment. There are several commercialized CGP assays with variable targeted genes, however, how large a panel should be used for breast cancer remains undetermined.
Methods
Triple negative breast cancer (TNBC) patients from the VGH-TAYLOR study were initially assayed by a medium-sized CGP panel (Oncomine Comprehensive Panel, OCP, v3), and the remaining nucleic acid specimens were re-sequenced with a large-sized CGP panel (TruSight Oncology 500, TSO500). Molecular profiling between the two sequencing panels was compared and reported.
Results
A total of 108 breast cancers were successfully assayed using both platforms and 272 variants were reported at least once by OCP or TSO500. Variants reported were among actionable genes (AKT1, BRCA1/2, PALB2, ERBB2, PIK3CA, PTEN) and TP53. Concordance rate between TSO500 and OCP was 34.6% and was enhanced to 58.9% after excluding polymorphisms, out-of-targeted region variants and those with low variant allele frequency (< 10%).
Conclusion
Only one-third of actionable mutations could be detected consistently between the medium- and the large-sized CGP panels using the default analytical pipelines, while extensive bioinformatics analyses improved variant calling consistency substantially. TSO500, the larger panel, detected more variants than OCP from the same set of actionable genes.