Kameda Masahiro, Otani Yoshihiro, Ichikawa Tomotsugu, Shimada Akira, Ichimura Koichi, Date Isao
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
World Neurosurg. 2017 May;101:817.e5-817.e14. doi: 10.1016/j.wneu.2017.02.026. Epub 2017 Feb 16.
The molecular diagnosis of brain tumors is important in classifying tumors and determining appropriate treatment. Congenital glioblastoma multiforme (GBM) is a rare tumor that occurs in infants, and the prognosis is poor. Approximately 60 patients diagnosed with congenital GBM have been reported. However, few reports have conducted molecular analyses of congenital GBM.
We describe 2 congenital GBM patients treated in our hospital, and report results of immunohistochemistry, fluorescent in situ hybridization (FISH), direct sequencing, and methylation analyses. Surgery was performed on both patients at 2 months old, and the cases were diagnosed as glioblastoma. Immunohistochemical staining, FISH, and direct sequencing were positive for glial fibrillary acidic protein and ATRX, partially positive for p53, showed no alteration of isocitrate dehydrogenase 1 R132H, H3F3A, HIST1H3B, and BRAF, and indicated no codeletion of 1p and 19q. Methylation analysis of 1 patient identified copy number aberrations of 4 genes: deletions of CDK6 and CDKN2A/B, and a fusion of MET. One patient received chemotherapy consisting of ranimustine, interferon-beta, carboplatin, and etoposide, whereas the other patient received chemotherapy with the modified Children's Cancer Group study-9921 protocol. Residual tumors in both patients were decreased, and they achieved 18-year- and 9-month progression-free survival, respectively. In addition, we reviewed 65 previously reported congenital GBM patients, and found they have better prognosis than pediatric and adult GBM, and long-term survival can be expected.
Congenital GBM demonstrates clinical and molecular characteristics that are different from those of pediatric or adult GBM.
脑肿瘤的分子诊断对于肿瘤分类和确定合适的治疗方法至关重要。先天性多形性胶质母细胞瘤（GBM）是一种发生于婴儿的罕见肿瘤，预后较差。据报道，大约有60例被诊断为先天性GBM的患者。然而，对先天性GBM进行分子分析的报道很少。
我们描述了在我院接受治疗的2例先天性GBM患者，并报告了免疫组织化学、荧光原位杂交（FISH）、直接测序和甲基化分析的结果。两名患者均在2个月大时接受了手术，病例被诊断为胶质母细胞瘤。免疫组织化学染色、FISH和直接测序显示胶质纤维酸性蛋白和ATRX呈阳性，p53呈部分阳性，异柠檬酸脱氢酶1 R132H、H3F3A、HIST1H3B和BRAF无改变，且1p和19q无共缺失。对1例患者的甲基化分析发现4个基因的拷贝数异常：CDK6和CDKN2A/B缺失，以及MET融合。1例患者接受了由司莫司汀、干扰素-β、卡铂和依托泊苷组成的化疗，而另1例患者接受了改良的儿童癌症研究组9921方案化疗。两名患者的残留肿瘤均减少，分别实现了18年和9个月的无进展生存期。此外，我们回顾了65例先前报道的先天性GBM患者，发现他们的预后比儿童和成人GBM更好，有望长期生存。
先天性GBM表现出与儿童或成人GBM不同的临床和分子特征。
