NOVEL GENETIC ABERRATIONS IN PEDIATRIC AND ADULT ASTROCYTOMAS

虽然很少有儿童星形细胞瘤的研究， 通过细胞遗传学或分子遗传学方法，已知成体 星形细胞瘤通常含有特征性染色体缺失和/或 癌基因扩增 因为许多高级别的成人星形细胞瘤 在基因上相当复杂和异质，这些肿瘤很可能 由多个致癌事件共同作用引起， 是恶性进展的必要条件 在一个初步的系列， 包括4例儿童病例，我们证实了克隆性染色体畸变 6例星形细胞瘤中有5例。 另一个有趣的发现是， 高级别组织学的儿童星形细胞瘤似乎 遗传复杂性和不稳定性比类似的成年人报告 肿瘤的 我们假设儿童的相对遗传简单性 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有关。 在拟定的研究中，我们将前瞻性评估特定染色体 儿童和成人星形细胞瘤中的畸变和遗传不稳定性。 将通过相关性评价这些结果的生物学相关性 组织病理学结果、总生存率和Ki-67增殖 指数. 将通过回顾性研究进一步评价生存趋势 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将是 绘制和表征与临床相关的遗传畸变， 儿童和成人星形细胞瘤。

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.