Comparative Brain Tumor Consortium

比较脑肿瘤联盟

• 批准号: 10486921
• 负责人: Amy Leblanc
• 金额: $ 9.3万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486921
• 关键词: Adult; Adult Glioma; Affect; American; Apoptosis; Area; Astrocytoma; Basic Science; Biopsy; Brain Neoplasms; CCR; Cancer Center; Canis familiaris; Catalogs; Cell Line; Characteristics; Childhood Glioma; Classification; Classification Scheme; Clinical; Clinical Trials; Collaborations; Companions; Comparative Pathology; Consensus; Data; Development; Diagnosis; Discipline; Disease; Early Diagnosis; Enrollment; Event; Excision; Expression Profiling; Extramural Activities; Face; Freezing; Funding; Future; Genomics; Glass; Glioma; Goals; Grant; Group Structure; Hematoxylin and Eosin Staining Method; Histologic; Histology; Histopathology; Human; Illinois; Image; Immunotherapeutic agent; Incidence; Income; Informatics; Infrastructure; Institution; Internal Medicine; Joints; Journals; Knowledge; Link; Magnetic Resonance Imaging; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of brain; Manuscripts; Medicine; Methylation; Minnesota; Modeling; Molecular; Molecular Profiling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Nature; Neuraxis; Neurologist; Neurology; Oncology; Operative Surgical Procedures; Outcome; PAC1 phosphatase; Paper; Pathologic; Pathology; Patient Care; Patients; Pharmacology; Physicians; Pituitary Neoplasms; Play; Positron-Emission Tomography; Pre-Clinical Model; Prevention; Procedures; Process; Publications; Publishing; Radiology Specialty; Reporting; Research; Research Personnel; Role; Slide; Specialist; Stains; Surveys; TP53 gene; Texas; The Jackson Laboratory; Time; Tissues; Training; Ultrasonography; United States National Institutes of Health; Universities; Update; Veterinarians; Veterinary Medicine; base; cancer clinical trial; college; comparative; disease natural history; drug development; drug discovery; exome; exome sequencing; experience; glioma cell line; high-throughput drug screening; human disease; human model; imaging agent; improved; improved outcome; interest; irradiation; meetings; member; meningioma; neuro-oncology; neuropathology; novel; oligodendroglioma; oncology program; pathology imaging; prospective; ranpirnase; small molecule; statistics; stem cells; transcriptome sequencing; tumor; working group

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 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.

COP 在 2018 年这项新举措的首次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病学杂志》正在审查一份出版物。病理学委员会由 14 名成员组成的联合兽医/医师神经病理学委员会组成，制定了更新的犬神经胶质瘤分级和分类方案，以促进各机构诊断的一致性，并改进与成人和儿童神经胶质瘤的比较。对大约 200 张苏木精和伊红染色玻璃载片 + 一组 5 个 IHC 标记物的所有亚型和级别的未接受过治疗的犬神经胶质瘤进行了回顾性病理学评估。 CBTC 成员还提议对至少 50 种符合新修订的分类标准的犬高级别神经胶质瘤进行基因组分析和表达谱分析，以便与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。该项目本质上既具有回顾性又具有前瞻性。对于回顾性部分，来自机构的速冻组织与来自经组织病理学证实的神经胶质瘤的配对储存的 FFPE 组织（已在新提出的分级和分类方案中得到确认）将进行全外显子组测序和 RNA 测序。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 Jackson 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，从一组重叠的犬神经胶质瘤中生成分子图谱，其中包括 WGS/WES/RNAseq 和甲基化图谱数据。序列信息将在准备好发表后立即进行信息学、处理和公开共享。我们还在该领域启动了几个其他项目，如下所列： 1. n = 100 例犬脑膜瘤的全外显子组和 RNA 测序（与加州大学戴维斯分校的 Peter Dickinson、UAB 的 M. Renee Chambers 和 Greg Tawa 合作） /NIH/NCATS 2. 美国兽医神经学家的调查工具，以了解犬脑肿瘤治疗的临床情况 3. P53 的高通量药物筛选w/t 犬和儿童神经胶质瘤细胞系 4. 在患有脑膜瘤的狗中进行新型 Capsize-3 激活小分子 (PAC-1) 的临床试验，该试验与新型凋亡报告 PET 成像剂的评估相关（与5. 与 NHLBI/IPDC、NCI/CCR/MIP 和伊利诺伊大学合作的关于参加脑肿瘤临床试验的犬的成像参数统一的 MRI 共识声明（手稿发表在《兽医放射学》和《兽医放射学》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 一起扩展 HTS 项目，包括在加州戴维斯大学生成的 5 个新的犬神经胶质瘤干细胞系，以及每两个月一次的 WebEx，以在感兴趣的 CBTC 成员之间提供持续的想法和项目交流。