NOVEL GENETIC ABERRATIONS IN PEDIATRIC AND ADULT ASTROCYTOMAS

尽管很少有儿童星形细胞瘤被用来研究 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的染色体缺失和/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性，这些肿瘤很可能 由多个致癌事件共同作用的结果，这些事件 对于完全恶性进展是必要的。在初步的系列中， 包括4个儿科病例，我们展示了克隆性染色体异常。 6例星形细胞瘤中有5例。另一个有趣的发现是 组织学级别高的儿童星形细胞瘤似乎较少 遗传复杂性和不稳定性比同类成人的报告要高 肿瘤。我们假设，儿科患者的相对遗传简单性 病例将有助于识别新的基因异常， 可能也与成人星形细胞瘤有关。 在拟议的研究中，我们将前瞻性地评估特定的染色体。 儿童和成人星形细胞瘤的异常和遗传不稳定性。 这些发现的生物学相关性将通过相关性进行评估。 有组织病理学发现，总存活率和Ki-67增殖 指数。生存趋势将通过回顾进一步评估 冰冻和/或石蜡包埋的分子细胞遗传学分析 星形细胞瘤标本。这些研究的最终目标将是 绘制和表征具有临床意义的遗传异常 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.