Molecular Diagnostics Core Laboratory

分子诊断核心实验室

• 批准号: 10487234
• 负责人: Liqiang Xi
• 金额: $ 90.35万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487234
• 关键词: American; Archives; B-Lymphocytes; BRAF gene; Biological Assay; Biological Markers; Blood; Bone Marrow; CCR; Cancer Patient; Capillary Electrophoresis; Cells; Classification; Clinical; Clinical Treatment; Clinical Trials; Collaborations; Complex; Consult; DNA; Detection; Diagnostic; Disease; Early Diagnosis; Eligibility Determination; Gene Expression; Gene Mutation; Genes; Genomics; Hematologic Neoplasms; Hematopathology; Histiocytic sarcoma; Human Herpesvirus 4; Human Herpesvirus 8; Human T-lymphotropic virus 1; Institutes; Intramural Research Program; Laboratories; Liquid substance; Lymphoproliferative Disorders; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of urinary bladder; Methylation; Modernization; Molecular; Molecular Biology; Molecular Diagnostic Testing; Mutation; Mutation Analysis; National Cancer Institute; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Needle biopsy procedure; Pathologic; Pathologist; Pathology; Patient Care Team; Patients; Pediatric Neoplasm; Performance; Play; Pleural; Process; Proteins; Quality Control; RNA; Reagent; Recurrence; Research; Research Personnel; Rest; Reverse Transcriptase Polymerase Chain Reaction; Role; Running; Sampling; Site; Specimen; Specimen Handling; Structure; Subgroup; T cell clonality; Technology; Test Result; Testing; Therapeutic; Tissues; Training and Education; Translational Research; United States National Institutes of Health; base; cancer subtypes; cell free DNA; childhood sarcoma; clinical Diagnosis; clinical center; clinically relevant; college; cost; digital; exome sequencing; instrument; melanoma; molecular diagnostics; molecular oncology; molecular pathology; molecular targeted therapies; multiplex assay; mutational status; neoplastic cell; novel; precision oncology; prognostic; programs; pyrosequencing; rare cancer; research clinical testing; symposium; transcriptome sequencing; treatment response; tumor DNA; tumor behavior; virus related cancer

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 FY21 (July 2020 - June 2021) the molecular diagnostics laboratory processed 3500 unique clinical samples from NCI/NIH patients (2413 are FFPE tissue cases, 1087 are blood, bone marrow, CSF, pleural fluid specimens). The lab extracted 3500 DNA and 976 RNA samples. While 1017 cases were performed with COMPASS NGS assays and 1200 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 6726 single or multiplex assays to continue 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, pyrosequencing. The assays we performed included tests to identify B and T-cell clonality, translocations associated with pediatric sarcomas, cancer associated viruses (e.g., EBV, HTLV1, HHV8), BRAF, MYD88 mutations from blood, bone marrow, and final needle biopsies. These assays support 46 NCI clinical trials and 27 other NIH institutes trials (from NHGRI, NHLBI, NINID, NIDDK, and Urgent_ICU). 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 researches 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 from blood on KingFisher Duo Prime and 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.

分子诊断科是目前唯一的CLIA和美国病理学院批准的临床实验室在NCI认证的病理材料从NIH患者进行分子肿瘤学检测。在2021财年（2020年7月至2021年6月），分子诊断实验室处理了来自NCI/NIH患者的3500份独特临床样本（2413份为FFPE组织病例，1087份为血液、骨髓、CSF、胸腔积液样本）。实验室提取了3500个DNA和976个RNA样本。其中1017例使用COMPASS NGS检测，1200例使用甲基化阵列检测，其余临床病例使用传统分子检测进行检测，以满足NCI和其他NIH研究所的临床需求。该实验室利用各种技术进行6726项单一或多重检测，以继续为病理学实验室和NIH临床中心的临床诊断和治疗服务，包括常规PCR，RT-PCR，qPCR，液滴数字PCR（ddPCR），毛细管电泳，焦磷酸测序。我们进行的测定包括鉴定B和T细胞克隆性、与儿科肉瘤相关的易位、癌症相关病毒（例如，EBV、HTLV 1、HHV 8）、BRAF、MYD 88突变。这些检测试剂盒支持46项NCI临床试验和27项其他NIH研究所试验（来自NHGRI、NHLBI、NINID、NIDDK和Urgent_ICU）。该实验室还进行了1000多次测试，用于每两年一次的CAP能力测试或替代能力测试，以及每周批次中每种PCR检测的质量控制（阳性、阴性、无模板对照）。临床检测的QC和QM性能约占核心实验室试剂成本的15-20%。通过向病理学家和临床团队提供分子检测结果，分子实验室负责病理学住院医师和研究员的培训和教育。每个第一年的居民/研究员轮流到分子实验室一个月。分子实验室和血液病理学科也参加了每周一次的分子签出会议。分子诊断实验室还支持NCI和NIH研究人员的许多转化研究。我们开发的核心技术之一是癌症患者的无细胞循环肿瘤DNA（ctDNA）检测。实验室继续对KingFisher Duo Prime和new QIAsymphony仪器上的血液游离DNA提取、其数量和质量以及ddPCR和NGS的超灵敏检测进行测试和评价。该计划是使用ctDNA作为治疗反应和早期检测复发的生物标志物。我们与CCR研究人员一起在不同的癌症亚型中开展了一些新的研究，包括黑色素瘤、肺癌、膀胱癌和胰腺癌。我们继续与Elaine Jaffe博士合作研究罕见的造血系统癌症，目前正在研究组织细胞肉瘤的分子生物学，利用Jaffe博士在其咨询实践中收集和存档的样本，并根据基因表达，疾病部位和突变状态确定了这些罕见癌症的新亚组。