Comparative Brain Tumor Consortium

缔约方会议在首次比较病理学方面取得了重大进展， 这一新举措在2018年，目前在审查的出版物杂志 神经病理学和实验神经学。病理学委员会，由一个联合 兽医/医生神经病理学委员会的14名成员，制定了一个更新的分级， 分类方案，以促进统一的诊断犬胶质瘤， 研究机构和改进与人类成人和儿童胶质瘤的比较。一 对约200个苏木精和伊红染色玻璃进行回顾性病理评估 切片+一组5种IHC标记物所有亚型和级别的未经治疗犬胶质瘤 已经进行了。CBTC成员还提出了基因组分析和表达 至少50只犬高级别胶质瘤符合这些新修订的 分类标准，以便与成人和儿童胶质瘤进行比较， 为犬患者产生潜在的药理学靶点。该项目将是双方 回顾性和前瞻性。对于回顾性部分，速冻组织 来自具有来自组织病理学证实的神经胶质肿瘤的配对库存FFPE组织的机构 在新提议的分级和分类制度中得到确认的， 进行全外显子组测序和RNA-seq.对于未来部分，CBTC成员 （德克萨斯A&M大学/MD安德森癌症中心、明尼苏达大学和 加州大学戴维斯分校）与杰克逊实验室的Roel Verhaak合作。Verhaak博士 正在与这些CBTC成员合作，他们通过P30 CC获得了NCI资助 补充机制，以从一组重叠的犬科动物中生成分子谱 神经胶质瘤，其中将包括WGS/WES/RNAseq和甲基化分析数据。序列 信息经过信息学处理，并通过国家癌症研究所公开共享 集成犬数据共享（ICDC），并发表在《癌细胞》上。我们还启动了 在这方面的其他几个项目，这是在这里列出：1。全外显子组和RNA测序 n = 100只犬脑膜瘤（与UC-Davis的Peter Dickinson合作，M. Renee UAB和Greg Tawa/NIH/NCATS 2的分庭。美国兽医神经学家调查工具 美国捕捉犬脑肿瘤管理的临床景观3。高通量药物 筛选P53 w/t犬和儿童胶质瘤细胞系4.一种小说的临床试验 capsize-3激活小分子（PAC-1）在患有脑膜瘤的狗中， 评估一种新的可报告骨质疏松的PET显像剂（与NHLBI/IPDC合作， NCI/CCR/MIP和伊利诺伊大学。5. MRI关于协调的共识声明 脑肿瘤临床试验中登记的狗的成像参数（手稿发表于 兽医放射学和超声）。2018年及以后拟议的新项目包括： 犬脑膜瘤的组织学和分子特征比较研究; 与NCATS一起扩展HTS项目，以纳入5种新的犬神经胶质瘤干细胞系 在加州大学戴维斯分校生成，以及双月WebEx，以提供持续的思想交流 CBTC成员之间的项目。

The COP has made significant progress on the inaugural comparative pathology effort for this new initiative in 2018, with a publication currently in review at the Journal of Neuropathology and Experimental Neurology. The pathology board, consisting of a joint veterinary/physician neuropathology commission of 14 members, 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 childhood gliomas. 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 childhood gliomas, 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, CBTC members (Texas A&M University/MD Anderson Cancer Center, University of Minnesota, and University of Califnornia @ Davis) have partnered with Roel Verhaak at the Jackson laboratory. Dr Verhaak is working with these CBTC members, whom have received NCI funding through a P30 CC supplemental mechanism, to generate molecular profiles from an overlapping set of canine gliomas, which will include WGS/WES/RNAseq and methylation profiling data. Sequence information was subjected to informatics, processed, and shared publicly through the NCI Integrated Canine Data Commons (ICDC) and published in Cancer Cell. We have also initiated several other projects in this area, which are listed here: 1. Whole-exome and RNA sequencing of n = 100 canine meningiomas (in collaboration with Peter Dickinson at UC-Davis, M. 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 childhood 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 published in Veterinary Radiology and Ultrasound). New projects proposed for 2018- beyond include: a companion comparative histologic and molecular characterization project in canine meningioma; extension of the HTS project with NCATS to include 5 new canine glioma stem cell lines generated at Univ of CA-Davis, and a bi-monthly WebEx to offer continuing exchange of ideas and projects among interested CBTC members.