Comparative Brain Tumor Consortium

比较脑肿瘤联盟

• 批准号: 9556680
• 负责人: Amy Leblanc
• 金额: $ 4.95万
• 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/9556680
• 关键词: Adult; Affect; American; Apoptosis; Area; Astrocytoma; Basic Science; Biopsy; Brain Neoplasms; CCR; Canis familiaris; Catalogs; Characteristics; Childhood; Childhood Glioma; Classification; Classification Scheme; Clinical; Clinical Trials; Collaborations; Collection; Comparative Pathology; Consensus; Data; Development; Diagnosis; Discipline; Disease; Early Diagnosis; Enrollment; Event; Excision; Face; Formalin; Freezing; Funding; Future; Genomics; Glass; Glioma; Goals; Group Structure; Hematoxylin and Eosin Staining Method; Histologic; Histology; Histopathology; Human; Illinois; Image; Incidence; Income; Informatics; Institution; Internal Medicine; Joints; Journals; Knowledge; Link; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Manuscripts; Medicine; Modeling; Molecular; Molecular Profiling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Nature; Neuraxis; Neurologist; Neurology; Operative Surgical Procedures; Outcome; PAC1 phosphatase; Paper; Pathologic; Pathology; Patient Care; Patients; Pharmacology; Physicians; Pituitary Neoplasms; Play; Positron-Emission Tomography; Pre-Clinical Model; Preclinical Drug Evaluation; Prevention; Private Practice; Procedures; Process; Publications; Publishing; RNA; Reporting; Research; Research Infrastructure; Research Personnel; Role; Sampling; Site; Slide; Specialist; Specimen; Staining method; Stains; Surveys; TP53 gene; Tissue Banks; Tissues; Training; United States National Institutes of Health; Universities; Update; Veterinarians; Veterinary Medicine; Work; base; biobank; college; comparative; disease natural history; drug development; drug discovery; exome sequencing; experience; follow-up; glioma cell line; human disease; imaging agent; improved; improved outcome; irradiation; meetings; member; meningioma; neuro-oncology; neuropathology; novel; oligodendroglioma; oncology; prospective; small molecule; statistics; transcriptome sequencing; tumor; working group

The COP has made significant progress on the inaugural comparative pathology effort for this new initiative in 2017. The pathology board, consisting of a joint veterinary/physician neuropathology commission of 14 members, has developed an updated grading and classification scheme for canine gliomas to promote uniformity in diagnosis across institutions and improve making comparisons with human adult and pediatric glial tumors. A retrospective pathologic assessment of approximately 200 hematoxylin and eosin stained glass slides + a panel of 5 IHC markers treatment-naive canine gliomas of all subtypes and grades has been conducted. The CBTC membership has also proposed genomic analyses and expression profiling of a minimum of 50 canine high-grade gliomas meeting these newly revised classification criteria to allow for comparison with human adult and pediatric glial tumors, and to generate potential pharmacologic targets for canine patients. This project will be both retrospective and prospective in nature. For the retrospective portion, snap-frozen tissue from institutions with paired banked FFPE tissue from histopathology-confirmed glial tumors that have been confirmed within the newly proposed grading and classification scheme, will be subjected to whole-exome sequencing and RNA-seq. For the prospective portion, kits and detailed SOPs will be distributed to selected sites, both academic institutions and private practices, for the collection of tumor specimens. Samples will be snap-frozen tissue or tissue in RNA-later and formalin-fixed tissue, stored at a central biobank location, and subjected to histopathological confirmation, whole-exome sequencing and RNA-sequencing as funding is available. Sequence information will be subjected to informatics, processed, and shared publicly as soon as publication-ready. The COP's role will be to coordinate collection of tissues and partner with an academic leader within the CBTC network to determine the optimal location for the sequencing and informatics work, and will provide programmatic support to the project. We have also initiated several other projects in this area, which are listed here: 1. Whole-exome sequencing of n = 50 canine meningiomas (in collaboration with Renee Chambers at UAB and Greg Tawa/NIH/NCATS 2. Survey instrument to veterinary neurologists in the US to capture the clinical landscape of canine brain tumor management 3. High-throughput drug screening of P53 w/t canine and pediatric glioma cell lines 4. A clinical trial of a novel capsize-3 activating small molecule (PAC-1) in dogs with meningioma, which is linked to assessment of a novel apoptosis-reporting PET imaging agent (in collaboration with NHLBI/IPDC, NCI/CCR/MIP, and University of Illinois. 5. MRI consensus statement on harmonization of imaging parameters for dogs enrolled in brain tumor clinical trials (manuscript in press). A follow up meeting of the CBTC membership is planned at NIH on Sept 18-19, 2017

缔约方会议在2017年为这一新倡议开展的首次比较病理学工作方面取得了重大进展。病理学委员会由14名成员组成的兽医/医生神经病理学联合委员会组成，已为犬神经胶质瘤制定了最新的分级和分类方案，以促进各机构诊断的统一性，并改善与成人和儿童神经胶质瘤的比较。对约200张苏木精和伊红染色的载玻片+一组5种IHC标记物的所有亚型和等级的未经治疗的犬胶质瘤进行了回顾性病理学评估。CBTC成员还提出了至少50个符合这些新修订的分类标准的犬高级别胶质瘤的基因组分析和表达谱分析，以与人类成人和儿童胶质瘤进行比较，并为犬患者产生潜在的药理学靶点。该项目将是回顾性和前瞻性的。对于回顾性部分，来自具有来自组织病理学确认的神经胶质肿瘤的配对库FFPE组织的机构的速冻组织（已在新提出的分级和分类方案中确认）将进行全外显子组测序和RNA-seq。对于前瞻性部分，将向选定的研究中心（学术机构和私人诊所）分发试剂盒和详细的SOP，以采集肿瘤标本。样本将是快速冷冻的组织或RNA后期和福尔马林固定组织中的组织，储存在中心生物库位置，并在资金可用时进行组织病理学确认、全外显子组测序和RNA测序。序列信息将进行信息学处理，并在出版准备就绪后立即公开共享。COP的作用将是协调组织的收集，并与CBTC网络内的学术领导者合作，以确定测序和信息学工作的最佳位置，并将为该项目提供计划支持。我们还在这一领域开展了其他几个项目，如下所列：1. n = 50只犬脑膜瘤的全外显子组测序（与UAB的Renee Chambers和Greg Tawa/NIH/NCATS 2.调查工具，以兽医神经学家在美国捕捉犬脑肿瘤管理的临床景观3。P53 w/t犬和小儿胶质瘤细胞系的高通量药物筛选4.一项在脑膜瘤犬中进行的新型capsize-3激活小分子（PAC-1）的临床试验，该试验与一种新型肿瘤报告PET成像剂的评估有关（与NHLBI/IPDC、NCI/CCR/MIP和伊利诺伊大学合作）。5.关于纳入脑肿瘤临床试验的犬的成像参数协调的MRI共识声明（印刷稿）。CBTC成员的后续会议计划于2017年9月18日至19日在NIH举行