We are excited to announce the results of the Archer® Research Challenge Grant. The goal of this grant was to encourage physicians, pathologists and researchers to ask challenging research questions that could be addressed with Archer targeted enrichment assays for next-generation sequencing.
Our hope was to provide a means to address these questions in environments where funding for clinical research is limited, in the form of 24 Archer kits of the awardee’s choosing as well as any necessary training from our Field Applications Specialists.
We received an outstanding number of high-quality grant applications from the United States and Europe. In fact, we received so many excellent applications that we extended the program to include 6 grant awards as well as 7 runners up.
A wide range of research projects were chosen, from novel fusion identification and cancer subtype characterization to the development of an RNA sequencing assay from liquid biopsy samples. Nearly half of the awarded kits will be used to study Sarcoma, and several others will be used to study hematologic malignancies, including AML, ALL and lymphoma. Lung and thyroid cancer will also be covered as well as gastric cancer.
The recipients of the Archer Research Challenge Grant are listed below.Competition Details
Dr. Enrique de Alava and his team aim to improve the characterization of Sarcoma subtypes by evaluating the accuracy and reproducibility of the FusionPlex Sarcoma kit to detect known and novel fusion transcripts in several well-characterized sarcoma subtype cohorts. As these fusions are traditionally detected by FISH or RT-PCR followed by Sanger sequencing, Dr. de Alava and his team will assess the concordance of the FusionPlex Sarcoma kit with these methods for each specific sarcoma subtype.
Dr. Ryma Benayed currently uses a hybrid-capture based DNA sequencing assay developed at Memorial Sloan Kettering, MSK-IMPACT, which successfully detects mutations but is limited in its ability to accurately detect gene fusions. She will be using a previously designed custom FusionPlex Solid Tumor kit to elucidate novel or inconclusive DNA rearrangements detected by MSK-IMPACT across an array of solid tumors.
Dr. Florian Haller is using the FusionPlex Sarcoma and Oncology Research kits to identify recurrent gene fusions in 4000 well-characterized sarcomas with the aim to identify subsets of sarcomas based on shared fusions and cytology. Dr. Haller will also screen undifferentiated spindle-cell sarcomas for clinically actionable fusions, as a subset of these sarcomas has recently been shown to harbor clinically actionable NTRK1 fusions.
Dr. Hans Morreau will be using Comprehensive Thyroid and Lung (CTL) FusionPlex and VariantPlex kits to test difficult to classify thyroid lesions for known and novel fusions in RNA and variants in DNA. The goal of this study is to improve the classification of thyroid lesions, which are difficult to classify based on morphology and immunohistochemistry alone, and which require different treatment modalities.
Dr. Russell Ryan will be using the Lymphoma FusionPlex kit for gene expression analysis and point mutation detection in Diffuse Large B Cell Lymphoma (DLBCL). The resulting gene expression and mutation profiles will then be used to classify DLBCL cases as either activated B cell (ABC) or germinal B cell (GBC) subtypes, which have significant therapeutic and prognostic differences.
Dr. Cecilia Yeung is evaluating Archer Blood Cancer Assays to identify rare known and unknown fusions in pediatric acute myeloid leukemia (AML). As this disease is heterogeneous with a wide variety of driver mutations and in some cases show rare fusions, Dr. Yeung and her collaborators plan to use these results to design tailor-made RT-PCR assays for disease monitoring in children with rare fusion AML.
Dr. Anne McLeer is using the FusionPlex ALK/RET/ROS1 v2 kit to detect both known and novel ALK fusions, as ALK fusions are clinically actionable in a subset at non-small cell lung cancer (NSCLC) and form fusion genes with multiple different partners. Dr. McLeer’s group recently observed a discordance between current methods to detect ALK fusions, FISH and IHC, and the Ion AmpliSeq™ RNA sequencing assay. However, the FusionPlex ALK/RET/ROS1 v2 kit detected novel ALK fusions in concordance with FISH and IHC. She will continue to evaluate the ability of the ALK/RET/ROS1 v2 kit to detect ALK fusions in a larger cohort of NSCLC cases and will ultimately investigate the role of fusion partner genes on crizotinib sensitivity.
Dr. Craig Mackinnon will compare targeted NGS approaches to detect relevant mutations in acute myeloid leukemia (AML) FFPE blood clot samples with a particular emphasis on FLT3 mutations and ITDs and CEBPα mutations. These mutations are challenging to detect and often require fresh tissue samples, as FFPE blood clot samples have particularly low tumor cellularity. Dr. Mackinnon will test AML-positive FFPE blood clot specimens with known mutations using the VariantPlex Core AML kit, the Ion AmpliSeq™ AML Panel and the TruSight™ Myeloid Sequencing Panel.
Stephanie Springborn will use the Comprehensive Thyroid and Lung (CTL) kits to demonstrate the clinical utility of comprehensive mutation profiling of non-small cell lung cancers (NSCLC), for which multiple targeted therapies already exist or are in development. NSCLC samples with known point mutations will be tested with the VariantPlex CTL kit and the Ion AmpliSeq™ Cancer Hotspot Panel to determine the relative accuracy of these two NGS-based methods for mutation detection in DNA. Furthermore, NSCLC samples with known fusions will be tested with the CTL FusionPlex kit.
Dr. Mary Chamberlin will use the Solid Tumor FusionPlex and VariantPlex kits for comprehensive mutation profiling of gastric cancer samples from Rwanda, where gastric cancer incidence and mortality rates are high compared to other parts of the world. As gastric cancer is highly heterogeneous, comprised of four distinct molecular subtypes, Rwandan and U.S. samples will be compared to identify potential regional differences in mutation profiles.
Merrida Childress is using the FusionPlex Oncology Research kit to identify known and novel fusions in inflammatory myofibroblastic tumor (IMT), a soft tissue sarcoma that primarily affects the pediatric population. Although about half of IMTs harbor clinically actionable ALK fusions, the molecular landscape of ALK-negative IMTs remains undefined. These results will be used to identify potential therapeutic targets in IMT, as well as to investigate the effect of identified fusion partners on tyrosine kinase inhibitor (TKI) sensitivity.
Dr. Leonardo Meza-Zepeda is investigating the ability of AMP-based NGS to detect fusion transcripts in exosomes and tumor-educated platelets in blood samples. He will be using the FusionPlex Sarcoma and ALK/RET/ROS1 kits to detect fusions in blood samples collected from sarcoma and lung cancer patients with known fusions.
Dr. Sara Dyer is evaluating the FusionPlex Acute Lymphoblastic Leukemia (ALL) kit for detection of clinically relevant gene fusions in ALL, which are routinely tested for diagnostic, prognostic and therapeutic purposes. Cytogenetic and sequential interphase FISH and RT-PCR are currently used to test for fusions in ALL, however these methods are limited both in their resolution and ability to detect multiple fusions in a cost effective manner and in a clinically relevant timeframe. Therefore, Dr. Dyer will assess the concordance of the FusionPlex ALL kit to detect fusions with these methods on bone marrow samples with known fusions, and will test whether the ALL kit can detect fusions that could not be detected by standard methods.
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