Development of FISH Molecular Diagnostics to support Clinical Trials at NCI

开发 FISH 分子诊断以支持 NCI 的临床试验

• 批准号: 8938526
• 负责人: Svetlana Pack
• 金额: $ 56.12万
• 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/8938526
• 关键词: 19q; Accreditation; Alveolar Soft Part Sarcoma; BCL2 gene; Biological Assay; Biopsy; Bladder; Brain Neoplasms; Breast; CCR; Cancer Patient; Cancer Vaccines; Certification; Childhood; Chromosomal Duplication; Chromosomal translocation; Chromosome abnormality; Chromosomes; Clinical; Clinical Trials; Collaborations; Communities; DNA Sequence Rearrangement; Decision Making; Detection; Development; Diagnostic; Disease; ERBB2 gene; EWSR1 gene; Epidermal Growth Factor Receptor; Event; Ewings sarcoma; FGFR1 gene; FLI1 gene; Fluorescent in Situ Hybridization; Follicular Lymphoma; Formalin; Gastrointestinal tract structure; Gene Amplification; Gene Expression; Genes; Hematologic Neoplasms; Hematopoietic Neoplasms; Housing; Image Analysis; Immunohistochemistry; Immunotherapy; In Situ Hybridization; Inflammatory Pseudotumor; Inherited; Kidney Neoplasms; Laboratories; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Malignant neoplasm of thyroid; Medicine; Methods; Microscope; Molecular; Molecular Profiling; Monitor; NTRK1 gene; Neoplasm Circulating Cells; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Outcome; PDGFRA gene; PIK3CA gene; Paraffin Embedding; Pathology; Patients; Pediatric Neoplasm; Pediatric Oncology; Protocols documentation; Renal carcinoma; Reporting; Research; Research Personnel; Sampling; Sensitivity and Specificity; Solid Neoplasm; Specificity; Spectral Karyotyping; Stomach; Survival Rate; Syndrome; TFE3 gene; Testing; Thick; Thymus Neoplasms; Tissues; Treatment Effectiveness; United States National Institutes of Health; Urologic Oncology; Vaccine Clinical Trial; Validation; Work; alternative treatment; base; c-myc Genes; cancer cell; clinically significant; fluorescence imaging; improved; lapatinib; large cell Diffuse non-Hodgkin' s lymphoma; malignant breast neoplasm; malignant stomach neoplasm; molecular oncology; molecular pathology; neuro-oncology; novel diagnostics; peripheral blood; research clinical testing; tool; tumor

The Chromosome Pathology Unit (CPU)was opened in 2010 to fulfill the need in the "in house" laboratory FISH tests required to support clinical trials at NCI. The official CAP accreditation and CLIA certification has been accomplished by the CPU team in November 22, 2010. From January 2011 the Lab started receiving clinical cases for FISH testing. The CPU performed more than 5,000 tests since its opening. This includes FISH assays for over 1120 clinical reported tests, over 5000 tests for probe validation and collaboration with LP and other NIH researchers. FISH diagnostics are an integral part of the Pathology molecular diagnostics currently offered by the Lab of Pathology. The sensitivity and specificity of FISH diagnostics was found to be near 100% in recent reports of CAP that puts them in front line among other available tests based on PCR and immunohistochemistry that have a long-known specificity problem. The Chromosome Pathology Unit (CPU) in the Laboratory of Pathology performs Fluorescence In Situ Hybridization (FISH) assays on formalin-fixed paraffin-embedded (FFPE) tissues to support active clinical trials at the NCI and NIH. The demand for this testing is high; the CPU receives orders for FISH tests on clinical tumor samples daily, and currently supports 17 clinical trials at the NCI. That includes requests from the entire community of CCR investigators: Molecular Oncology Branch, Surgery Branch, Office of the Director, Pediatric Oncology Branch, Neuro-Oncology Branch, Urologic Oncology Branch. The active test menu includes FISH assays for clinically significant chromosomal translocations and amplification events in solid tumors and hematologic malignancies. The developed/ validated tests include Her-2 amplification in Breast, Lung, and GI tract cancer, c-myc translocation in Burkitt and Diffuse Large B Cell Lymphoma, BCL2 translocation in Follicular Lymphoma, 1p/19q deletion tests for brain tumors, ALK translocation in lung cancer and inflammatory myofibroblastic tumors, FGFR1, PDGFRA and PIK3A amplification in lung cancer, NTRK1 amplification in thymic tumors, TFE-3 translocation in renal tumors, alveolar soft part sarcoma, EWSR1/FLI1 and FOXO1translocations in pediatric tumors (Ewing's sarcoma and Rabdomyosarcoma), etc. In addition, the CPU is currently developing and validating ten new FISH tests for additional frequent chromosomal abnormalities in cancers that have been requested by NCI investigators. Among the tests in the pipeline are RET rearrangements in thyroid cancer, ERG translocation in prostate cancer, TFE-B gene translocation in renal tumors (responsible for 30% of pediatric kidney cancer). The CPU has been working on developing novel diagnostics that would significantly advance currently existing approaches in cancer clinical testing. One of them is Isolation and Molecular Profiling of the Circulating Tumor Cells (CTCs) from the peripheral blood of cancer patients as an alternative non-invasive biopsy method for detection and monitoring tumor metastatic disease and treatment efficiency. The Unit has been equipped as state-of-the art laboratory that includes a new automated Fluorescence imaging workstation Duet from BioView. Inc, Zeiss epifluorescence microscope with the ApoTome feature that allows FISH analysis and imaging of thick tissue sections, SKY-cube for spectral karyotyping - a modern tool for the detection of chromosomal translocations in cancer cells and various hereditary syndromes.

染色体病理学单元 (CPU) 于 2010 年成立，以满足支持 NCI 临床试验所需的“内部”实验室 FISH 测试的需求。 CPU团队已于2010年11月22日完成CAP官方认可和CLIA认证。从2011年1月开始，实验室开始接收FISH检测的临床病例。该CPU自启用以来已进行了5000多次测试。其中包括超过 1120 项临床报告测试的 FISH 检测、超过 5000 项探针验证测试以及与 LP 和其他 NIH 研究人员的合作。 FISH 诊断是病理学实验室目前提供的病理学分子诊断的一个组成部分。最近的 CAP 报告发现，FISH 诊断的灵敏度和特异性接近 100%，这使得 FISH 诊断在其他基于 PCR 和免疫组织化学的现有检测中处于领先地位，而这些检测存在着长期已知的特异性问题。病理学实验室的染色体病理学单位 (CPU) 对福尔马林固定石蜡包埋 (FFPE) 组织进行荧光原位杂交 (FISH) 检测，以支持 NCI 和 NIH 的活跃临床试验。此测试的需求很高； CPU 每天都会收到对临床肿瘤样本进行 FISH 检测的订单，目前支持 NCI 的 17 项临床试验。这包括来自整个 CCR 研究人员社区的请求：分子肿瘤学分支、外科分支、主任办公室、儿科肿瘤学分支、神经肿瘤学分支、泌尿肿瘤学分支。主动测试菜单包括针对实体瘤和血液恶性肿瘤中具有临床意义的染色体易位和扩增事件的 FISH 检测。开发/验证的测试包括乳腺癌、肺癌和胃肠道癌的 Her-2 扩增、Burkitt 和弥漫性大 B 细胞淋巴瘤的 c-myc 易位、滤泡性淋巴瘤的 BCL2 易位、脑肿瘤的 1p/19q 缺失测试、ALK 易位在肺癌和炎性肌纤维母细胞肿瘤中，在肺癌中 FGFR1、PDGFRA 和 PIK3A 扩增，在胸腺肿瘤中 NTRK1 扩增，肾肿瘤中的 TFE-3 易位、肺泡软组织肉瘤、儿科肿瘤（尤文氏肉瘤和横纹肌肉瘤）中的 EWSR1/FLI1 和 FOXO1 易位等。此外，CPU 目前正在开发和验证 10 种新的 FISH 检测，用于检测儿童中其他常见的染色体异常。 NCI 研究人员要求的癌症。正在进行的测试包括甲状腺癌中的 RET 重排、前列腺癌中的 ERG 易位、肾肿瘤中的 TFE-B 基因易位（导致 30% 的儿童肾癌）。 CPU 一直致力于开发新颖的诊断方法，以显着推进现有的癌症临床测试方法。其中之一是从癌症患者外周血中分离和分子分析循环肿瘤细胞（CTC），作为检测和监测肿瘤转移性疾病和治疗效率的替代非侵入性活检方法。该装置配备了最先进的实验室，其中包括 BioView 的新型自动化荧光成像工作站 Duet。 Inc. 的蔡司落射荧光显微镜具有 ApoTome 功能，可对厚组织切片进行 FISH 分析和成像，SKY-cube 用于光谱核型分析 - 一种用于检测癌细胞染色体易位和各种遗传综合征的现代工具。

项目成果

ER/PR positive epidermotropic primary cutaneous eccrine carcinoma as a cutaneous manifestation of MEN 2B.

ER/PR 阳性亲表皮性原发性皮肤小汗腺癌作为 MEN 2B 的皮肤表现。

• DOI: 10.1016/j.jaad.2013.08.001
• 发表时间: 2013
• 期刊: Journal of the American Academy of Dermatology
• 影响因子: 13.8
• 作者: Aung,PhyuP;Ballester,LeomarY;Abdullaev,Zied;Pack,SvetlanaD;Cummins,DeborahL;Mahalingam,Meera
• 通讯作者: Mahalingam,Meera

ERG expression in epithelioid sarcoma: a diagnostic pitfall.

• DOI: 10.1097/pas.0b013e31828de23a
• 发表时间: 2013-10
• 期刊: The American journal of surgical pathology
• 作者: Miettinen M;Wang Z;Sarlomo-Rikala M;Abdullaev Z;Pack SD;Fetsch JF
• 通讯作者: Fetsch JF

Spinal cord glioneuronal tumor with neuropil-like islands with 1p/19q deletion in an adult with low-grade cerebral oligodendroglioma.

• DOI: 10.1007/s11060-011-0760-9
• 发表时间: 2012-04
• 期刊: Journal of neuro-oncology
• 影响因子: 3.9
• 作者: Fraum TJ;Barak S;Pack S;Lonser RR;Fine HA;Quezado M;Iwamoto FM
• 通讯作者: Iwamoto FM

Primary subcutaneous spindle cell Ewing sarcoma with strong S100 expression and EWSR1-FLI1 fusion: a case report.

具有强 S100 表达和 EWSR1-FLI1 融合的原发性皮下梭形细胞尤文肉瘤：病例报告。

• DOI: 10.2350/14-03-1454-cr.1
• 发表时间: 2014
• 期刊: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
• 作者: Arnold,MichaelA;Ballester,LeomarY;Pack,SvetlanaD;Abdullaev,Ziedulla;Merchant,Melinda;Tsokos,MariaG
• 通讯作者: Tsokos,MariaG

Two Cases of Spinal, Extraosseous, Intradural Ewing's sarcoma/Peripheral Neuroectodermal Tumor: Radiologic, Pathologic, and Molecular Analysis.

• DOI: 10.4103/2156-7514.126050
• 发表时间: 2014
• 期刊: Journal of clinical imaging science
• 影响因子: 0.9
• 作者: Mardekian SK;Gandhe A;Miettinen M;Pack S;Curtis MT;Abdullaev Z
• 通讯作者: Abdullaev Z