TP53 获得性功能突变在多灶性脑胶母细胞瘤中的作用。
The role of TP53 gain-of-function mutation in multifocal glioblastoma.
机构信息
Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
出版信息
J Neurooncol. 2020 Mar;147(1):37-47. doi: 10.1007/s11060-019-03318-5. Epub 2020 Jan 30.
PURPOSE
The phenotypic and genotypic landscapes in multifocal glioblastoma (MF GBM) cases can vary greatly among lesions. In a MF GBM patient, the rapid development of a secondary lesion was investigated to determine if a unique genetic signature could account for the apparent increased malignancy of this lesion.
METHODS
The primary (G52) and secondary (G53) tumours were resected to develop patient derived models followed by functional assays and multiplatform molecular profiling.
RESULTS
Molecular profiling revealed G52 was wild-type for TP53 while G53 presented with a TP53 missense mutation. Functional studies demonstrated increased proliferation, migration, invasion and colony formation in G53.
CONCLUSION
This data suggests that the TP53 mutation led to gain-of-function phenotypes and resulted in greater overall oncogenic potential of G53.
目的
多灶性胶质母细胞瘤（MF GBM）病例中的表型和基因型图谱在病变之间可能有很大差异。在一位 MF GBM 患者中，研究了继发性病变的快速发展，以确定是否存在独特的遗传特征可以解释该病变明显增加的恶性程度。
方法
切除原发性（G52）和继发性（G53）肿瘤，以开发患者来源的模型，然后进行功能测定和多平台分子分析。
结果
分子分析显示 G52 的 TP53 为野生型，而 G53 则存在 TP53 错义突变。功能研究表明 G53 中增殖、迁移、侵袭和集落形成能力增加。
结论
该数据表明，TP53 突变导致了获得性功能表型，并导致 G53 的整体致癌潜力增加。
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