ABSTRACT

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.

For Research Use Only. Not for use in diagnostics procedures.

About ArcherDX

ArcherDX is a leading genomics company democratizing precision oncology. We offer a suite of research products that are powered by our proprietary Anchored Multiplex PCR (AMP™) chemistry, including FusionPlex^®, VariantPlex^®, LiquidPlex™ and Immunoverse™. Additionally, we are developing IVD products for solid tumor biomarker identification and Personalized Cancer Monitoring (PCM™) but which are not yet approved for clinical or diagnostic use.

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ABOUT THE SPEAKER

Sarinya Kongpetch, Ph.D.

Assistant Professor, Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Thailand

Assistant Professor, Sarinya Kongpetch is the lecturer and the Principle Investigator at the Department of Pharmacology, Faculty of Medicine at Khon Kaen University in Thailand. She obtained her BSc in Pharmaceutical Sciences in 2006 and Ph.D. in 2012 from Khon Kaen University.

During her post-doctoral training at the laboratory of cancer epigenome, National Cancer Centre Singapore, she has led the study of genomic research focusing on fusion genes. Concurrently, her research interest is to improve the clinical outcome of cholangiocarcinoma (CCA) patients through exploring the possible targeting molecules. To gain insight into the genomic biomarker, she also obtained the research grant from Thailand Research Fund to study on the FGFR genomic alteration in CCA.

Recently, Dr. Sarinya, along with Singapore collaborating scientists in the field of cancer genomic research, published their work on the prevalence of FGFR fusion genes in cholangiocarcinoma by using the new technique called “Anchored Multiplex PCR” RNA-sequencing.