The Molecular Diagnostics Section is currently the only CLIA and College of American Pathology approved clinical laboratory within the NCI certified for performing molecular oncology testing on pathology materials from NIH patients. In FY19 (July 2018 - June 2019) the molecular diagnostics laboratory processed 2585 unique clinical samples from NCI/NIH patients, and performed 7949 clinical tests. The laboratory utilizes a variety of technologies to perform 7337 single or multiplex assays including conventional DNA PCR, RT-PCR, qPCR, droplet digital PCR, allele suppression PCR, capillary electrophoresis, pyrosequencing, bisulfite pyrosequencing. The assays we perform include tests to identify B and T-cell clonality, translocations associated with pediatric sarcomas (e.g., EWS-FLI-1, EWS-ERG, EWS-WT-1, PAX-7/FKHD, PAX-3/FKHD, SYT-SSX-1, and SYT-SSX-2), cancer associated viruses (e.g., EBV, HTLV, HHV-8), and BRAF, MYD88 mutations. Quantitative PCR is performed for HTLV 1/2 to follow viral load in ATL clinical trials. MGMT methylation analysis is performed using bisulfite pyrosequencing to provide predictive information regarding response to temozolomide in the glioblastoma setting. The laboratory performed 612 next-generation sequencing (NGS) tests, Primary CNS Tumor Panel and Oncomine Comprehensive Assay v3 for other cancer types. The laboratory continued the program in the use of circulating tumor DNA (ctDNA) as a biomarker for disease response and early detection. These two efforts (NGS and ctDNA) are linked as the genotyping is not only used to identify potential therapeutic targets, but it is also used to identify targets for the circulating DNA (ctDNA) studies. Early studies targeting BRAF V600E ctDNA in melanoma patients (collaboration with Dr. S. Rosenberg) indicated the potential use of this technology in predicting responses to cellular immunotherapy, and recurrence. We have expanded our initial studies with Dr. Rosenberg in melanoma to a wide range of other TIL treated tumors (breast, ovary, colon) targeting patient specific exome and transcriptome sequence identified targets, with similar results. We have initiated new studies with other investigators in diverse cancer subtypes including uveal melanoma, lung, bladder, and pancreatic cancer. Early results with Dr. Guha in lung cancer has shown the sensitivity of the technology in tracing disease activity, and identifying treatment failures weeks to months before progressive disease became clinically evident. We have continued to study rare hematopoietic cancers in collaboration with Dr. Elaine Jaffe and are currently investigating the molecular biology of Histiocytic Sarcoma taking advantage of the samples collected and archived by Dr. Jaffe in her consult practice, and have identified novel subgroups of these rare cancers based on gene expression, disease site and mutational status. The molecular diagnostics laboratory also supports many translational research of NCI and NIH researchers. While the lab is continuing current clinical service to CCR clinical communities and collaborative research projects, the biggest achievement is to start COMPASS program and established the infrastructure to prepare sequencing at least 1000 patients per year. We have setup the laboratories from tumor samples to enable processing of DNA/RNA extraction, equipped the labs for library preparation to sequencing to analysis, hired wet bench and dry bench (bioinformatics) scientists and technologists. We have validated the TruSight Oncology 500 Gene Panel (DNA mutations for 523 genes, TMB, MSI, and RNA fusion detections) and are preparing to launch as a clinical test. We also started evaluation of whole exome DNA and RNA sequencing. With these technologies, LP will be at the cutting edge of clinical cancer genomics and will serve as an important resource for the CCR.
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