Comparative Brain Tumor Consortium

缔约方会议在2018年这项新倡议的首次比较病理学工作方面取得了重大进展，目前正在《神经病理学和实验神经病学杂志》上发表评论。病理委员会由14名成员组成的兽医/医生神经病理学联合委员会组成，为犬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，并改善与人类成人和儿童胶质瘤的比较。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，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博士正在与这些通过P30 CC补充机制获得NCI资助的CBTC成员合作，从一组重叠的犬胶质瘤中生成分子图谱，其中包括WGS/WES/RNAseq和甲基化分析数据。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。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犬和儿童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（手稿发表在Veterinary Radiology and Ultrasound）。2018年以后提出的新项目包括：犬脑膜瘤的同伴比较组织学和分子表征项目;与NCATS合作的HTS项目的扩展，包括在加州大学戴维斯分校产生的5种新的犬胶质瘤干细胞系，以及每两个月一次的WebEx，以提供感兴趣的CBTC成员之间的持续交流。

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 will be subjected to informatics, processed, and shared publicly as soon as publication-ready. 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 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.