The Molecular Diagnostics Laboratory 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 2015 the molecular diagnostics laboratory processed 1786 unique clinical samples from NCI/NIH patients, and performed 6287 tests. The laboratory utilizes a variety of technologies to perform these assays including conventional DNA PCR, RT-PCR, qPCR, allele suppression PCR, capillary electrophoresis, pyrosequencing, bisulfite pyrosequencing, and small panel next generation sequencing (NGS). The assays we perform include tests to identify B and T-cell clonality, lymphoma specific translocations (e.g., BCL-1/IG, BCL-2/IG), 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 mutations associated with a variety of cancers (e.g., EGFR, KRAS, NRAS, BRAF, PIK3CA, IDH1/2, AKT, MYD88, ERBB2, STAT3, and STAT5b). Quantitative PCR is performed for HTLV 1/2 to follow viral load in ATL clinical trials, and for the EGFRvIII to assess expression of this cancer-specific transcript for clinical trial eligibility. MGMT methylation analysis is performed using bisulfite pyrosequencing to provide predictive information regarding response to temozolomide in the glioblastoma setting. IDH1/2 is performed to assist in glioma diagnosis and as a prognostic marker. The laboratory also offers a 50 gene NGS panel for clinical use, interrogating some of the more commonly involved genes in cancer. This panel is currently our standard CLIA level mutation panel when it is necessary to assess mutations in more than one gene as is the case in lung cancer. The laboratory's developmental research effort has been focused on the application of next generation sequencing (NGS) technologies to assist in cancer genotyping and diagnostics. In addition to the 50 gene panel currently in clinical use, the laboratory is developing more focused tumor specific panels that will better cover the mutational spectra of specific tumor types. The laboratory has also initiated a 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 studies. Early studies in melanoma patients (collaboration with Dr. S. Rosenberg) indicate the potential use of this technology in predicting responses to immunotherapy and recurrence. We continue to extend these studies in cutaneous melanoma and have initiated new studies in in other cancers including uveal melanoma, and lung cancer. Among our more notable laboratory initiated studies reported in 2015 was the identification of JAK/STAT and RAS family mutations in intestinal T-cell lymphomas, a rare lymphoma subtype. This was one of the first molecular level studies of ITCL, and the first to identify the presence of RAS mutations. The molecular diagnostics laboratory also supports translational research of NCI and NIH researchers. Among the NCI and NIH investigators and clinicians that have utilized the laboratory's resources in 2015 are: Dr. A. Apolo (NCI), Dr. Fred Barr (NCI), Dr. Austin Barrett (NHLBI), Dr. William Gahl (NHGRI), Dr. Steven Holland (NIAID), Dr. Elaine Jaffe (NCI), Dr. Udai Kammula (NCI) Dr. Daniel Kastner (NHGRI) Dr. Amy Klion (NHLBI) Dr. Robert Kreitman (NCI) Dr. Markku Mietinnen (NCI), Dr. Kenneth Olivier (NIAID), Dr. Stefania Pittaluga (NCI), Dr. Martha Quezado (NCI), Dr. Koneti Rao (NIAID) ,Dr. Steven Rosenberg (NCI), Dr. Helen Su (NHLBI), Dr. Jeffrey Cohen (NIAID), Dr. Thomas Uldrick (NCI), Dr. Gulbu Uzel (NIAID), Dr. Katherine Warren (NCI), Dr. Wyndham Wilson (NCI), Dr. James Yang (NCI), Dr. Neil Young (NHLBI).
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