Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage
Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage
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DOI：
10.1007/s10014-019-00355-w
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发表时间：
2019-10-26
影响因子：
3.3
通讯作者：
Kurotaki, Hidekachi
中科院分区：
文献类型：
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作者：
Ogawa, Kaoru;Kurose, Akira;Kurotaki, Hidekachi
巨细胞胶质母细胞瘤（GC-GBM）由细胞核多形性的大细胞组成。与GC-GBM相比，我们将单调小GBM （MS-GBM）定义为由单调小细胞核的小细胞组成的GBM，并比较了DNA损伤及其他病理特征。GC-GBM侵袭很小（< 2mm），有局灶性肉瘤。TERTp在GC-GBM中为野生型，在MS-GBM中为突变型。OLIG2在MS-GBM中的表达显著高于MS-GBM (77%， GC-GBM为7%)（P < 0.01）。GC-GBM的DNA双链断裂率显著高于MS-GBM (P < 0.01) （GC-GBM为76%，MS-GBM为15%）。几乎所有GC-GBM大细胞均行dsb。因此，GC-GBM中显著的DSBs可能是由先天的低干性特征诱导的，随后是有丝分裂滑脱，导致多倍体和大的多形性细胞核。我们得出结论，GC-GBM是一种独特的胶质瘤亚型，其特征是易受DNA损伤，野生型TERTp和较低的OLIG2功能可能诱导了这一特征。值得注意的是，即使是具有严重dsb的大多型核也显示Ki67阳性，这提醒病理学家对Ki67阳性的解释，因为具有严重dsb的大核细胞不能被识别为促进肿瘤侵袭性的增殖细胞。
Giant cell glioblastoma (GC-GBM) consists of large cells with pleomorphic nuclei. As a contrast to GC-GBM, we defined monotonous small GBM (MS-GBM) as GBM that consists of small cells with monotonous small nuclei, and compared the DNA damage as well as other pathological features. GC-GBM showed minimal invasion (< 2 mm) and focal sarcomatous areas. TERTp was wild type in GC-GBM but mutant in MS-GBM. OLIG2 expression was significantly higher in MS-GBM (P < 0.01) (77% in MS-GBM and 7% in GC-GBM). GC-GBM showed significantly higher DNA double-strand breaks (DSBs) compared with MS-GBM (P < 0.01) (76% in GC-GBM and 15% in MS-GBM). Nearly, all large cells in GC-GBM underwent DSBs. Thus, significant DSBs in GC-GBM might be induced by an innate lesser stemness characteristic and be followed by mitotic slippage, resulting in polyploidization and the large pleomorphic nuclei. We conclude that GC-GBM is a distinctive subtype of glioma characterized by its vulnerability to DNA damage and that wild-type TERTp and lower OLIG2 function might induce this feature. Notably, even large pleomorphic nuclei with severe DSBs demonstrated Ki67 positivity, which alerts pathologists to the interpretation of Ki67 positivity, because cells with large nuclei undergoing severe DSBs cannot be recognized as proliferating cells that contribute to tumor aggressiveness.