Comparative Brain Tumor Consortium

缔约方会议在2018年这一新倡议的首期比较病理学工作方面取得了重大进展，目前《神经病理学和实验神经学杂志》正在审查一份出版物。病理委员会由14名成员组成的兽医/医生联合神经病理委员会组成，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。对近200张苏木精-伊红染色玻片，一组5种IHC标记物治疗所有亚型和分级的初治犬脑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。在未来的部分，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)已与杰克逊实验室的Roel Verhaak合作。Verhaak博士正在与这些CBTC成员合作，这些成员通过P30 CC补充机制获得了NCI的资助，以生成一组重叠的犬脑胶质瘤的分子图谱，其中将包括WGS/WES/RNAseq和甲基化图谱数据。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。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成像参数协调的MRI共识声明(手稿发表在《兽医放射学和超声》上)。2018年以后提出的新项目包括：犬脑膜瘤的配套比较组织学和分子表征项目；与NCATS的HTS项目扩展到包括CA-Davis大学培育的5个新的犬脑胶质瘤干细胞系；以及一个双月刊WebEx，在感兴趣的CBTC成员之间提供持续的想法和项目交流。

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 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, 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 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 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.