Inherited genetics of adult diffuse glioma and polygenic risk scores-a review.

IF 2.4 Q2 CLINICAL NEUROLOGY
Jeanette E Eckel-Passow, Daniel H Lachance, Paul A Decker, Thomas M Kollmeyer, Matthew L Kosel, Kristen L Drucker, Susan Slager, Margaret Wrensch, W Oliver Tobin, Robert B Jenkins
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引用次数: 1

Abstract

Knowledge about inherited and acquired genetics of adult diffuse glioma has expanded significantly over the past decade. Genomewide association studies (GWAS) stratified by histologic subtype identified six germline variants that were associated specifically with glioblastoma (GBM) and 12 that were associated with lower grade glioma. A GWAS performed using the 2016 WHO criteria, stratifying patients by IDH mutation and 1p/19q codeletion (as well as TERT promoter mutation), discovered that many of the known variants are associated with specific WHO glioma subtypes. In addition, the GWAS stratified by molecular group identified two additional novel regions: variants in D2HGDH that were associated with tumors that had an IDH mutation and a variant near FAM20C that was associated with tumors that had both IDH mutation and 1p/19q codeletion. The results of these germline associations have been used to calculate polygenic risk scores, from which to estimate relative and absolute risk of overall glioma and risk of specific glioma subtypes. We will review the concept of polygenic risk models and their potential clinical utility, as well as discuss the published adult diffuse glioma polygenic risk models. To date, these prior genetic studies have been done on European populations. Using the published glioma polygenic risk model, we show that the genetic associations published to date do not generalize across genetic ancestries, demonstrating that genetic studies need to be done on more diverse populations.

Abstract Image

成人弥漫性胶质瘤的遗传遗传学和多基因风险评分综述。
在过去的十年中,关于成人弥漫性胶质瘤的遗传和获得性遗传学的知识有了显著的扩展。按组织学亚型分层的全基因组关联研究(GWAS)鉴定出6种生殖系变异与胶质母细胞瘤(GBM)特异性相关,12种与低级别胶质瘤相关。使用2016年WHO标准进行的GWAS,通过IDH突变和1p/19q编码(以及TERT启动子突变)对患者进行分层,发现许多已知变异与特定的WHO胶质瘤亚型相关。此外,按分子组分层的GWAS发现了另外两个新区域:与具有IDH突变的肿瘤相关的D2HGDH变异和与具有IDH突变和1p/19q密码缺失的肿瘤相关的FAM20C附近的变异。这些种系关联的结果已被用于计算多基因风险评分,从中估计总体胶质瘤的相对和绝对风险以及特定胶质瘤亚型的风险。我们将回顾多基因风险模型的概念及其潜在的临床应用,并讨论已发表的成人弥漫性胶质瘤多基因风险模型。迄今为止,这些先前的基因研究都是在欧洲人群中进行的。使用已发表的神经胶质瘤多基因风险模型,我们表明迄今为止发表的遗传关联并不能在遗传祖先中推广,这表明需要在更多样化的人群中进行遗传研究。
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来源期刊
Neuro-oncology practice
Neuro-oncology practice CLINICAL NEUROLOGY-
CiteScore
5.30
自引率
11.10%
发文量
92
期刊介绍: Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving
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