McDonald Malcolm F, Gopakumar Sricharan, Juratli Tareq A, Eyüpoglu Ilker Y, Rao Ganesh, Mandel Jacob J, Jalali Ali
Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
Acta Neuropathol Commun. 2025 Jan 16;13(1):9. doi: 10.1186/s40478-024-01900-1.
Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences and initial tumors, supporting a common origin. Discontiguous recurrences were more likely to be hypermutated compared to contiguous recurrences (p = 0.038). Analysis of 2 glioblastoma cases with discontiguous recurrence at a collaborating institution also exhibited hypermutation. In conclusion, discontiguous glioblastoma recurrences share a common origin with the initial tumor and are more likely to be hypermutated than contiguous recurrences.
胶质母细胞瘤是最致命的原发性脑肿瘤，这主要归因于治疗后该疾病不可避免的复发。虽然大多数复发是局部性的，但患者很少出现新的非连续性胶质母细胞瘤病灶。目前对于非连续性复发的基因特征了解甚少。在我们的机构数据库中，我们对22例初发和复发的异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤患者进行了靶向外显子组测序。根据磁共振成像（MRI）上T2液体衰减反转恢复序列（FLAIR）信号与疾病初始部位是否存在连接，将复发分为连续性或非连续性。外显子组分析揭示了非连续性复发与初始肿瘤之间共享的驱动突变和乘客突变，支持共同起源。与连续性复发相比，非连续性复发更可能发生高突变（p = 0.038）。对合作机构的2例非连续性复发的胶质母细胞瘤病例进行分析也显示出高突变。总之，非连续性胶质母细胞瘤复发与初始肿瘤有共同起源，并且比连续性复发更可能发生高突变。
