Comparative Brain Tumor Consortium

2018年，COP在这项新计划的首次比较病理学工作中取得了重大进展，目前在《神经病理学和实验神经病学杂志》上发表了一篇论文。病理学委员会由14名成员组成的兽医/医师神经病理学联合委员会，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个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，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谱，其中将包括WGS/WES/RNAseq和甲基化谱数据。序列信息经过信息学处理，并通过NCI集成犬类数据共享（ICDC）公开共享，并发表在《癌细胞》杂志上。我们还在这方面启动了其他几个项目，列在这里：1。n = 100只犬脑膜瘤的全外外子组和RNA测序（与加州大学戴维斯分校的Peter Dickinson， UAB的M. 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。犬和儿童胶质瘤细胞系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狗的成像参数统一的MRI共识声明（手稿发表在《兽医放射学和超声》上）。2018年及以后的新项目包括：犬脑膜瘤的比较组织学和分子表征项目；扩展与NCATS的HTS项目，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，以及双月WebEx，以便在感兴趣的CBTC成员之间继续交流思想和项目。

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.