Giunti Laura, Pantaleo Marilena, Sardi Iacopo, Provenzano Aldesia, Magi Alberto, Cardellicchio Stefania, Castiglione Francesca, Tattini Lorenzo, Novara Francesca, Buccoliero Anna Maria, de Martino Maurizio, Genitori Lorenzo, Zuffardi Orsetta, Giglio Sabrina
Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy.
Neuro-Oncology Unit, Department of Pediatrics, Meyer Children's Hospital Florence, Italy.
Am J Cancer Res. 2014 May 26;4(3):293-303. eCollection 2014.
Glioblastoma (GBM) is a very aggressive and lethal brain tumor with poor prognosis. Despite new treatment strategies, patients' median survival is still less than 1 year in most cases. Few studies have focused exclusively on this disease in children and most of our understanding of the disease process and its clinical outcome has come from studies on malignant gliomas in childhood, combining children with the diagnosis of GBM with other pediatric patients harboring high grade malignant tumors other than GBM. In this study we investigated, using array-CGH platforms, children (median age of 9 years) affected by GBM (WHO-grade IV). We identified recurrent Copy Number Alterations demonstrating that different chromosome regions are involved, in various combinations. These observations suggest a condition of strong genomic instability. Since cancer is an acquired disease and inherited factors play a significant role, we compared for the first time the constitutional Copy Number Variations with the Copy Number Alterations found in tumor biopsy. We speculate that genes included in the recurrent 9p21.3 and 16p13.3 deletions and 1q32.1-q44 duplication play a crucial role for tumorigenesis and/or progression. In particular we suggest that the A2BP1 gene (16p13.3) is one possible culprit of the disease. Given the rarity of the disease, the poor quality and quantity of bioptic material and the scarcity of data in the literature, our findings may better elucidate the genomic background of these tumors. The recognition of candidate genes underlying this disease could then improve treatment strategies for this devastating tumor.
胶质母细胞瘤（GBM）是一种极具侵袭性和致命性的脑肿瘤，预后较差。尽管有新的治疗策略，但在大多数情况下，患者的中位生存期仍不足1年。很少有研究专门针对儿童期的这种疾病，我们对该疾病进程及其临床结局的大部分了解来自于儿童期恶性胶质瘤的研究，这些研究将诊断为GBM的儿童与患有除GBM以外的其他高级别恶性肿瘤的儿科患者合并在一起。在本研究中，我们使用阵列比较基因组杂交（array-CGH）平台，对受GBM影响（世界卫生组织IV级）的儿童（中位年龄9岁）进行了调查。我们确定了复发性拷贝数改变，表明不同的染色体区域以各种组合方式参与其中。这些观察结果提示存在强烈的基因组不稳定性。由于癌症是一种后天获得性疾病且遗传因素起重要作用，我们首次将染色体组拷贝数变异与肿瘤活检中发现拷贝数改变进行了比较。我们推测，9号染色体短臂2区1带3亚带（9p21.3）和16号染色体短臂1区3带3亚带（16p13.3）的复发性缺失以及1号染色体长臂3区2带1亚带到4区4带（1q32.1-q44）的重复中所包含的基因在肿瘤发生和/或进展中起关键作用。特别是，我们认为A2BP1基因（位于16p13.3）可能是该疾病的一个罪魁祸首。鉴于该疾病的罕见性、活检材料质量和数量较差以及文献中数据稀缺，我们的研究结果可能会更好地阐明这些肿瘤的基因组背景。识别该疾病潜在的候选基因可能会改善针对这种毁灭性肿瘤的治疗策略。
