Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan,
Acta Neuropathol. 2015 Jun;129(6):789-808. doi: 10.1007/s00401-015-1439-7. Epub 2015 May 15.
Diffusely infiltrating astrocytomas include diffuse astrocytomas WHO grade II and anaplastic astrocytomas WHO grade III and are classified under astrocytic tumours according to the current WHO Classification. Although the patients generally have longer survival as compared to those with glioblastoma, the timing of inevitable malignant progression ultimately determines the prognosis. Recent advances in molecular genetics have uncovered that histopathologically diagnosed astrocytomas may consist of two genetically different groups of tumours. The majority of diffusely infiltrating astrocytomas regardless of WHO grade have concurrent mutations of IDH1 or IDH2, TP53 and ATRX. Among these astrocytomas, no other genetic markers that may distinguish grade II and grade III tumours have been identified. Those astrocytomas without IDH mutation tend to have a distinct genotype and a poor prognosis comparable to that of glioblastomas. On the other hand, diffuse astrocytomas that arise in children do not harbour IDH/TP53 mutations, but instead display mutations of BRAF or structural alterations involving MYB/MYBL1 or FGFR1. A molecular classification may thus help delineate diffusely infiltrating astrocytomas into distinct pathogenic and prognostic groups, which could aid in determining individualised therapeutic strategies.
弥漫性浸润性星形细胞瘤包括弥漫性星形细胞瘤（WHO 分级 II 级）和间变性星形细胞瘤（WHO 分级 III 级），根据目前的 WHO 分类，它们被归类为星形细胞瘤。虽然与胶质母细胞瘤相比，这些患者的总体生存时间更长，但不可避免的恶性进展的时间最终决定了预后。最近的分子遗传学进展揭示了组织病理学诊断的星形细胞瘤可能由两种遗传上不同的肿瘤群组成。大多数弥漫性浸润性星形细胞瘤，无论 WHO 分级如何，都存在 IDH1 或 IDH2、TP53 和 ATRX 的同时突变。在这些星形细胞瘤中，尚未发现其他可能区分 II 级和 III 级肿瘤的遗传标志物。那些没有 IDH 突变的星形细胞瘤往往具有独特的基因型和与胶质母细胞瘤相当的不良预后。另一方面，发生在儿童中的弥漫性星形细胞瘤不携带 IDH/TP53 突变，但显示 BRAF 突变或涉及 MYB/MYBL1 或 FGFR1 的结构改变。因此，分子分类可以帮助将弥漫性浸润性星形细胞瘤划分为不同的发病机制和预后组，这有助于确定个体化的治疗策略。
