Molecular Diagnostics Core Laboratory

分子诊断核心实验室

• 批准号: 10703044
• 负责人: Liqiang Xi
• 金额: $ 206.89万
• 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/10703044
• 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 Child Health and Human Development; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; 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; Saliva; 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 center; clinical diagnosis; 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 FY22 (July 2021 - June 2022) the molecular diagnostics laboratory processed 4661 unique clinical samples from NCI/NIH patients (3418 are FFPE tissue cases, 1243 are blood, bone marrow, CSF, pleural fluid, saliva specimens). The lab extracted 4590 DNA and 1203 RNA samples. While 1376 cases were performed with COMPASS NGS assays and 1940 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 8393 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 42 NCI clinical trials and 65 other NIH institutes trials (from CC, NEI, NHGRI, NHLBI, NINID, NICHD, HIDCR, 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 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.

分子诊断科目前是 NCI 内唯一获得 CLIA 和美国病理学院批准的临床实验室，可对 NIH 患者的病理材料进行分子肿瘤学检测。在 2022 财年（2021 年 7 月至 2022 年 6 月），分子诊断实验室处理了来自 NCI/NIH 患者的 4661 份独特临床样本（3418 份是 FFPE 组织病例，1243 份是血液、骨髓、脑脊液、胸膜液、唾液样本）。该实验室提取了 4590 个 DNA 样本和 1203 个 RNA 样本。其中 1376 例采用 COMPASS NGS 检测，1940 例采用甲基化芯片检测，其余临床病例采用传统分子检测，以满足 NCI 和其他 NIH 机构的临床需求。该实验室利用多种技术进行8393次单一或多重检测，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、微滴数字PCR（ddPCR）、毛细管电泳、焦磷酸测序。我们进行的检测包括鉴定 B 细胞和 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、HTLV1、HHV8）、血液、骨髓中的 BRAF、MYD88 突变以及最终的针吸活检。这些检测支持 42 个 NCI 临床试验和 65 个其他 NIH 机构试验（来自 CC、NEI、NHGRI、NHLBI、NINID、NICHD、HIDCR、NIMH 和 NINDS）。该实验室还针对每两年一次的 CAP 能力或替代能力测试、每周批次的每个 PCR 检测进行了 1000 多次测试。 临床检测的质量管理绩效约占核心实验室试剂成本的 15-20%。分子实验室负责向病理学家和临床团队提供分子检测结果以进行患者护理，并负责病理住院医师和研究员的培训和教育。每个第一年的住院医师/研究员都会轮流到分子实验室一个月。分子实验室和血液病理学科还参加每周举行的分子签核会议。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。该实验室继续测试和评估 KingFisher Duo Prime 和新型 QIAsymphony 仪器从血液中提取的游离 DNA、其数量和质量，以及使用 ddPCR 和 NGS 进行超灵敏检测。该程序是使用 ctDNA 作为治疗反应和早期检测复发的生物标志物。我们与 CCR 研究人员一起针对多种癌症亚型（包括黑色素瘤、肺癌、膀胱癌和胰腺癌）启动了一些新研究。我们继续与 Elaine Jaffe 博士合作研究罕见的造血系统癌症，目前正在利用收集到的样本研究组织细胞肉瘤的分子生物学， Jaffe 博士在她的咨询实践中存档，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。