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三维核端粒分析作为少突胶质细胞瘤复发的生物标志物:一项初步研究。

Three-Dimensional Nuclear Telomere Profiling as a Biomarker for Recurrence in Oligodendrogliomas: A Pilot Study.

机构信息

Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC J1H 5N4, Canada.

Departments of Physiology and Pathophysiology, Rady Faculty of Health Sciences, Cell Biology, Research Institute of Oncology and Hematology (RIOH), CancerCare Manitoba (CCMB), The Genomic Centre for Cancer Research and Diagnosis (GCCRD), The University of Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada.

出版信息

Int J Mol Sci. 2020 Nov 12;21(22):8539. doi: 10.3390/ijms21228539.

Abstract

Mechanisms of recurrence in oligodendrogliomas are poorly understood. Recurrence might be driven by telomere dysfunction-mediated genomic instability. In a pilot study, we investigated ten patients with oligodendrogliomas at the time of diagnosis (first surgery) and after recurrence (second surgery) using three-dimensional nuclear telomere analysis performed with quantitative software TeloView (Telo Genomics Corp, Toronto, Ontario, Canada). 1p/19q deletion status of each patient was determined by fluorescent in situ hybridization on touch preparation slides. We found that a very specific 3D telomeric profile was associated with two pathways of recurrence in oligodendrogliomas independent of their 1p/19q status: a first group of 8 patients displayed significantly different 3D telomere profiles between both surgeries ( 0.0001). Their recurrence happened at a mean of 231.375 ± 117.42 days and a median time to progression (TTP) of 239 days, a period defined as short-term recurrence; and a second group of three patients displayed identical 3D telomere profiles between both surgery samples ( > 0.05). Their recurrence happened at a mean of 960.666 ± 86.19 days and a median TTP of 930 days, a period defined as long-term recurrence. Our results suggest a potential link between nuclear telomere architecture and telomere dysfunction with time to recurrence in oligodendrogliomas, independently of the 1p/19q status.

摘要

少突胶质细胞瘤的复发机制尚不清楚。复发可能是由端粒功能障碍导致的基因组不稳定性驱动的。在一项初步研究中,我们使用定量软件 TeloView(加拿大安大略省多伦多市 Telo Genomics 公司)对 10 名初诊(第一次手术)和复发(第二次手术)的少突胶质细胞瘤患者进行了三维核端粒分析。通过荧光原位杂交技术在触摸制备载玻片上检测每位患者的 1p/19q 缺失状态。我们发现,一种非常特定的三维端粒谱与少突胶质细胞瘤的两种复发途径有关,与它们的 1p/19q 状态无关:第一组 8 名患者在两次手术之间显示出明显不同的三维端粒谱( 0.0001)。他们的复发发生在平均 231.375 ± 117.42 天和中位进展时间(TTP)为 239 天,这段时间定义为短期复发;第二组 3 名患者在两次手术样本之间显示出相同的三维端粒谱( > 0.05)。他们的复发发生在平均 960.666 ± 86.19 天和中位 TTP 为 930 天,这段时间定义为长期复发。我们的研究结果表明,核端粒结构与端粒功能障碍之间存在潜在联系,与 1p/19q 状态无关,与少突胶质细胞瘤的复发时间有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b247/7696868/59f37506d466/ijms-21-08539-g001.jpg

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