University Hospital of Ioannina, Neurosurgical Research Institute, University of Ioannina School of Medicine, University Campus, Ioannina 45110, Greece.
Neuro Oncol. 2010 Jan;12(1):104-13. doi: 10.1093/neuonc/nop011. Epub 2009 Nov 23.
In gliomas, germline gene alterations play a significant role during malignant transformation of progenitor glial cells, at least for families with occurrence of multiple cancers or with specific hereditary cancer syndromes. Scientific evidence during the last few years has revealed several constitutive genetic abnormalities that may influence glioma formation. These germline abnormalities are manifested as either gene polymorphisms or hemizygous mutations of key regulatory genes that are involved either in DNA repair or in apoptosis. Such changes, among others, include hemizygous alterations of the neurofibromatosis 1 (NF1) and p53 genes that are involved in apoptotic pathways, and alterations in multiple DNA repair genes such as mismatch repair (MMR) genes, x-ray cross-complementary genes (XRCC), and O6-methylguanine-DNA methyltransferase (MGMT) genes. Subsequent cellular changes include somatic mutations in cell cycle regulatory genes and genes involved in angiogenesis and invasion, leading eventually to tumor formation in various stages. Future molecular diagnosis may identify new genomic regions that could harbor genes important for glioma predisposition and aid in the early diagnosis of these patients and genetic counseling of their families.
在神经胶质瘤中，胚系基因改变在祖细胞胶质细胞的恶性转化过程中起重要作用，至少在发生多种癌症或具有特定遗传性癌症综合征的家族中是如此。在过去几年中，科学证据揭示了几种可能影响神经胶质瘤形成的固有遗传异常。这些胚系异常表现为参与 DNA 修复或细胞凋亡的关键调节基因的基因多态性或杂合性突变。这些变化包括参与细胞凋亡途径的神经纤维瘤病 1（NF1）和 p53 基因的杂合性改变，以及错配修复（MMR）基因、X 射线交叉互补基因（XRCC）和 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）等多个 DNA 修复基因的改变。随后的细胞变化包括细胞周期调节基因和参与血管生成和侵袭的基因的体细胞突变，最终导致不同阶段的肿瘤形成。未来的分子诊断可能会确定可能包含对神经胶质瘤易感性重要的基因的新基因组区域，并有助于这些患者的早期诊断和遗传咨询。
