Comparative Brain Tumor Consortium

缔约方会议在2017年为这一新倡议开展的首批比较病理学工作方面取得了重大进展。由14名成员组成的兽医/内科联合神经病理委员会组成的病理委员会制定了最新的犬脑胶质瘤分级和分类方案，以促进跨机构诊断的一致性，并改进与人类成人和儿科胶质瘤的比较。对大约200例苏木精-伊红染色玻片+5种IHC标记物治疗所有亚型和分级的初生犬胶质瘤进行了回顾性病理评估。CBTC成员还建议对至少50个符合这些新修订的分类标准的犬类高级别胶质瘤进行基因组分析和表达谱分析，以便与人类成人和儿童神经胶质瘤进行比较，并为犬类患者产生潜在的药理学靶点。该项目将既具有追溯性，又具有前瞻性。对于回顾部分，来自机构的快速冷冻组织与来自组织病理学确认的胶质肿瘤的成对银行FFPE组织，已在新提出的分级和分类方案中得到确认，将接受完整外显子组测序和RNA-SEQ。对于预期的部分，将向选定的地点分发试剂盒和详细的标准操作规程，用于收集肿瘤标本，包括学术机构和私人诊所。样本将是快速冷冻的组织或RNA稍后和福尔马林固定的组织，存储在中央生物库位置，并在资金可用时接受组织病理学确认、整个外显子组测序和RNA测序。序列信息将接受信息学处理，并在发布准备就绪后立即公开共享。缔约方会议的作用将是协调组织的收集，并与CBTC网络内的一位学术领袖合作，以确定排序和信息学工作的最佳地点，并将为该项目提供方案支助。我们还在这一领域启动了其他几个项目，如下所列：1.对n=50只狗脑膜瘤进行全外显子测序(与UAB和Greg Tawa/NIH/NCATS的Renee Chambers合作)2.向美国兽医神经学家调查仪器以了解犬脑肿瘤的临床情况3.对狗和儿童胶质瘤细胞系P53进行高通量药物筛选4.在患有脑膜瘤的狗身上进行一种新的capize-3激活小分子(PAC-1)的临床试验，这与评估一种新的报告细胞凋亡的PET显像剂有关(与NHLBI/IPDC合作，NCI/CCR/MIP和伊利诺伊大学。5.关于纳入脑瘤临床试验的狗的磁共振成像参数协调的MRI共识声明(手稿在印刷中)。CBTC成员的后续会议计划于2017年9月18日至19日在美国国立卫生研究院举行

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