Comparative Brain Tumor Consortium

缔约方会议在2017年这一新倡议的首次比较病理学工作方面取得了重大进展。病理学委员会由一个由14名成员组成的兽医/医师神经病理学联合委员会组成，已经制定了犬胶质瘤的最新分级和分类方案，以促进各机构诊断的统一性，并改进与人类成人和儿童胶质瘤的比较。对大约200例苏木精和伊红染色玻片+一组5种免疫组化标记物进行了回顾性病理评估，对所有亚型和级别的犬胶质瘤进行了治疗。CBTC成员还提出了至少50种犬高级别胶质瘤的基因组分析和表达谱分析，以满足这些新修订的分类标准，以便与人类成人和儿童神经胶质瘤进行比较，并为犬患者产生潜在的药理学靶点。这个项目将是回顾性和前瞻性的性质。对于回顾性部分，来自机构的快速冷冻组织与来自组织病理学证实的神经胶质肿瘤的配对储存的FFPE组织，这些组织已在新提出的分级和分类方案中得到证实，将进行全外显子组测序和RNA-seq。对于未来的部分，试剂盒和详细的标准操作规程将分发到选定的地点，包括学术机构和私人诊所，用于收集肿瘤标本。样品将是速冻组织或RNA-later组织和福尔马林固定组织，储存在中央生物库位置，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。一旦准备好发表，序列信息将进行信息学处理，并公开共享。COP的作用将是协调组织的收集，并与CBTC网络中的学术领导者合作，以确定测序和信息学工作的最佳地点，并将为该项目提供规划支持。我们还在这方面启动了其他几个项目，列在这里：1。n = 50犬脑膜瘤的全外外子组测序（与UAB的Renee Chambers和Greg Tawa/NIH/NCATS合作）调查仪器在美国兽医神经科医生捕捉临床景观犬脑肿瘤管理3。犬和小儿胶质瘤细胞系P53的高通量药物筛选一项新型capsi3 -3激活小分子（PAC-1）在脑膜瘤犬中的临床试验，这与一种新型凋亡报告PET显像剂的评估有关（与NHLBI/IPDC， NCI/CCR/MIP和伊利诺伊大学合作）。参与脑肿瘤临床试验的犬的MRI成像参数协调一致的共识声明（手稿已出版）。CBTC成员后续会议计划于2017年9月18日至19日在NIH举行

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