NOVEL GENETIC ABERRATIONS IN PEDIATRIC AND ADULT ASTROCYTOMAS

儿童和成人星形细胞瘤中的新遗传畸变

• 批准号: 3783275
• 负责人: JONATHAN A FLETCHER
• 金额: --
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 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/3783275
• 关键词: astrocytoma; child (0-11); cytogenetics; gene mutation; human subject; human tissue; molecular oncology; molecular pathology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer invasiveness; pediatric neoplasm /cancer; prognosis

Although very few pediatric astrocytomas have been studied using cytogenetic or molecular genetic methods, it is known that adult astrocytomas often contain characteristic chromosome deletions and/or oncogene amplification. Because many high-grade adult astrocytomas are quite complex and heterogeneous genetically, it is likely that these tumors result from multiple oncogenetic events, acting in concert, that are necessary for full malignant progression. In a preliminary series that included 4 pediatric cases, we demonstrated clonal chromosome aberrations in 5 of 6 astrocytomas. An interesting secondary finding was that pediatric astrocytomas with high-grade histology appeared to have less genetic complexity and instability than that reported for similar adult tumors. We hypothesize that the relative genetic simplicity in pediatric cases will facilitate identification of novel genetic aberrations that might be relevant, as well, in adult astrocytomas. In the proposed studies, we will prospectively assess specific chromosome aberrations and genetic instability in pediatric and adult astrocytomas. The biologic relevance of these findings will be evaluated by correlation with histopathologic findings, overall survival, and Ki-67 proliferative index. Survival trends will be evaluated further by retrospective molecular cytogenetic analyses or frozen and/or paraffin-embedded astrocytoma specimens. The ultimate goal of these studies will be to fine map and characterize genetic aberrations which have clinical relevance in pediatric and adult astrocytomas.

尽管很少有儿童星形细胞瘤使用 细胞遗传学或分子遗传学方法，已知成人 星形细胞瘤通常含有特征性染色体缺失和/或 癌基因扩增。 因为许多高级别成人星形细胞瘤是 相当复杂和异质的遗传，这些肿瘤很可能 多种致癌事件共同作用的结果， 完全恶性进展所必需的。 在初步系列中 包括 4 个儿科病例，我们证明了克隆染色体畸变 6 个星形细胞瘤中的 5 个。 一个有趣的次要发现是 具有高级别组织学的儿童星形细胞瘤似乎较少 与报道的类似成人相比，遗传复杂性和不稳定性 肿瘤。 我们假设儿科的遗传相对简单 病例将有助于识别新的遗传畸变 可能也与成人星形细胞瘤相关。 在拟议的研究中，我们将前瞻性地评估特定染色体 儿童和成人星形细胞瘤的畸变和遗传不稳定性。 这些发现的生物学相关性将通过相关性进行评估 组织病理学结果、总生存率和 Ki-67 增殖 指数。 生存趋势将通过回顾性进一步评估 分子细胞遗传学分析或冷冻和/或石蜡包埋 星形细胞瘤标本。 这些研究的最终目标是改善 绘制并表征具有临床相关性的遗传畸变 儿童和成人星形细胞瘤。