28 September| Online
Fusion genes have been recognized as driver events during tumorigenesis for decades, with efficacies facilitated in clinical diagnosis and targeted therapy. The tumor specific event of fusion genes to neoplastic tissues and their oncogenic functionalities during carcinogenesis make them promising tools in the battle against cancer. Based on studies of the BCR-ABL oncogene, a targeted therapy, imatinib, was developed, which directly targeted the ABL kinase in addition to a few other kinases. This now created a predictive test, as well as an indicator of therapeutic response.
With advances in sequencing technologies and computational biology, a surge in the identification of fusion genes has accelerated clinical translation of these internal markers into biomarkers with clinical utility. High-throughput sequencing technologies, whole-genome, whole-exome and RNA sequencing facilitate the detection of novel fusions in tumors. However, they are impractical with respect to cost and efficiency in the context of clinical molecular diagnostic. Here we employed a targeted RNA sequencing approach with low RNA input requirements. Anchored Multiplex PCR (AMP™)-based enrichment was used to rapidly identify a broad range of gene fusions. AMP is a target-enrichment technology that significantly increases the sensitivity of gene fusion detection by RNA-seq, enabling detection of chimeric transcripts with single-molecule resolution.
Recently, FGFR fusions have generated significant interest as potential biomarkers for therapeutic and clinical molecular diagnostics in various cancers, including the biliary cancer or cholangiocarcinoma. Here we performed AMP target enrichment RNA-sequencing of FGFR1-3, validated by FISH and Sanger sequencing, in 121 fluke-associated and 95 non-fluke-associated cholangiocarcinoma (CCA) tumors.
Speaker:
Sarinya Kongpetch, Ph.D.
