Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS 975, Inserm U 975, CNRS, UMR 7225, Université Pierre et Marie Curie, Paris, France (A.A., Y.M, C.C., B.B., K.M., K.H.-X., M.S., J.-Y.D., A.I.); Department of Neuropathology (H.A., K.M.); Department of Neurology 2-Mazarin (F.L.-D., K.H.-X., M.S., J.-Y.D., A.I.); Department of Neurosurgery, AP-HP, Groupe Hospitalier Pitié-Salpêtriére, Paris, France (L.C.); Department of Neurology (H.F.v.T., J.C.R.); Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands (I.S., P.W., B.Y.); Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands (P.W.).
Neuro Oncol. 2014 Mar;16(3):400-8. doi: 10.1093/neuonc/not227. Epub 2013 Dec 12.
Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs.
We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis.
Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs.
Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
弥漫性低级别胶质瘤（LGG）是成人胶质细胞瘤的一个异质性亚组。染色体（chr）臂 1p/19q 缺失和 IDH 突变已被证明与少突胶质细胞表型和更好的预后密切相关。我们试图在非 1p/19q 缺失的 LGG 中鉴定相关的生物标志物。
我们使用基因组芯片、微卫星分析、IDH 测序、MGMT 启动子甲基化检测和 p53 表达分析对 126 例 LGG 进行了回顾性特征分析。
我们的研究证实，1p/19q 缺失与 p53 过表达互斥，与以下因素相关：（i）更好的预后，（ii）少突胶质细胞表型，（iii）MGMT 启动子甲基化，和（iv）IDH 突变。有趣的是，1p/19q 缺失的肿瘤在诊断时出现在年龄较大的患者中。我们的研究表明，非 1p/19q 缺失的 LGG 可分为 5 个主要的基因组亚组：（i）11p 缺失，（ii）19q 缺失，（iii）7 号染色体增益，（iv）19 号染色体增益，和（v）未分类。在非 1p/19q 缺失的 LGG 中，我们证明：（i）11p 缺失与星形细胞瘤表型相关，具有独立的负预后价值，（ii）19q 缺失降低了 IDH 突变的有利预后价值。我们的发现在一个独立的 98 例 LGG 队列中得到了验证。
在非 1p/19q 缺失的 LGG 中已经确定了新的基因组实体和生物标志物。我们的发现可能有助于对非 1p/19q 缺失的 LGG 进行分层，有助于未来对治疗进行个体化。需要进一步的前瞻性研究来支持我们的发现。
