Molecular Diagnostics Core Laboratory

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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 FY23 (July 2022 - June 2023) the molecular diagnostics laboratory processed 5553 unique clinical samples from NCI/NIH patients (4140 are FFPE tissue cases, 1431 are blood, bone marrow, CSF, pleural fluid, saliva specimens). The lab extracted 4709 DNA and 1339 RNA samples. While 1742 cases were performed with COMPASS NGS assays and 2725 cases were performed with Methylation Arrays, the rest of clinical cases were tested with traditional molecular tests to meet clinical needs from NCI and other NIH institutes. The laboratory utilizes a variety of technologies to perform near 10,000 single or multiplex assays every year to serve the Lab of Pathology and the NIH Clinical Center for clinical diagnosis and treatments, including conventional PCR, RT-PCR, qPCR, droplet digital PCR (ddPCR), capillary electrophoresis. The assays we performed included tests to identify B and T-cell clonality, cancer associated viruses (e.g., EBV, HTLV1, HHV8), BRAF, MYD88 mutations from blood, bone marrow, and final needle biopsies. These assays support 49 NCI clinical trials and 77 other NIH institutes trials (from CC, NEI, NHGRI, NHLBI, NIAID, NIAMS, NICHD, NIDCR, NIDDK, NIEHS, NIMH, and NINDS. The lab also performed over 1000 tests for bi-annual CAP proficiency or alternative proficiency tests, quality controls (positive, negative, no template controls) for each PCR assay in weekly batch. QC and QM performance for clinical testing took about 15-20% of the core laboratory's reagent costs. With delivering molecular test results to pathologists and clinical teams for patient cares, the molecular lab is responsible for training and education of pathology residents and fellows. Each of the first-year resident/fellows rotated to the molecular lab for one months. The molecular lab and Hematopathology Section also join running a weekly molecular sign-out conference. The molecular diagnostics laboratory also supports many translational research from NCI and NIH researchers. One of core technologies we developed was cell-free circulating tumor DNA (ctDNA) detection in cancer patients. The laboratory continued to test and evaluate extraction of cell-free DNA with the new QIAsymphony instrument, its quantity and quality, and ultrasensitive detection with ddPCR and NGS. The program was to use ctDNA as a biomarker for treatment response and early detection of recurrence. We have initiated some new studies with CCR investigators in diverse cancer subtypes including melanoma, lung, bladder, and pancreatic cancer. 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. We are also working to establish a clinically-focused Tumor Transcriptomics program. This program (SYNTHESIS: SYNthetic leThality to matcH patiEnts through tranScriptomIcS) will build on two existing foundations: (1) the existing NCICOMPASS Program housed in the Laboratory of Pathology, which provides CLIA-certified sequencing services of CC patients and, (2) the computational expertise developed in the CCR Cancer Data Science synthetic rescues (SR) patient stratification approaches (SELECT). The close CSDL-LP collaboration to initiate the SYNTHESIS program provides a unique opportunity for CCR clinician-investigators to evaluate and operationalize SL/SR-based transcriptomics approaches in clinical trials for our patients.