A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.
A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.
复制标题
DOI：
10.3390/cancers13174299
复制
发表时间：
2021-08-26
期刊：
影响因子：
5.2
通讯作者：
Bouley RA
中科院分区：
文献类型：
--
作者：
Pappula AL;Rasheed S;Mirzaei G;Petreaca RC;Bouley RA
异柠檬酸脱氢酶 1 (IDH1) 基因存在体细胞突变的神经胶质瘤患者比野生型基因型患者的预后和总生存率明显更好。据推测，IDH1 突变发生在细胞转化过程的早期，并导致进一步的遗传不稳定。对癌症体细胞突变目录 (COSMIC) 数据库中的神经胶质瘤患者进行全基因组分析，以对 IDH1 突变型与 IDH1 野生型患者的遗传差异进行分类。这种分类将有助于更好地了解这种特定突变如何影响神经胶质瘤的基因组成以及由此产生的预后。确定了与改善预后相关的共突变和基因表达水平的关键差异。神经胶质瘤分为两种主要疾病亚型：星形细胞瘤或少突胶质细胞瘤，由于预后和总生存率的显着差异，它们被表征为 IDH（异柠檬酸脱氢酶）野生型或 IDH 突变型。在这里，我们使用癌症体细胞突变目录 (COSMIC) 数据库研究了 IDH1 突变神经胶质瘤的遗传背景。在星形细胞瘤患者中，我们发现 IDH1 经常与 TP53、ATRX、AMBRA1、PREX1 和 NOTCH1 共突变，但不与 CHEK2、EGFR、PTEN 或锌指转录因子 ZNF429 共突变。通过癌症相关变异分析工具包 (CRAVAT)，这些基因中观察到的大多数突变被进一步证实为驱动因素或致病突变。基因表达分析显示 DRG2 和 MSN 表达下调，两者均促进细胞增殖和侵袭。 IDH1 突变型星形细胞瘤患者中 NDRG3 和 KCNB1 等基因也显着过度表达。我们得出的结论是，IDH1 突变神经胶质瘤的特点是显着的基因变化，这可能有助于神经胶质瘤患者更好的预后。
Glioma patients that present a somatic mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a significantly better prognosis and overall survival than patients with the wild-type genotype. An IDH1 mutation is hypothesized to occur early during cellular transformation and leads to further genetic instability. A genome-wide profiling of glioma patients in the Catalogue of Somatic Mutations in Cancer (COSMIC) database was performed to classify the genetic differences in IDH1-mutant versus IDH1-wildtype patients. This classification will aid in a better understanding of how this specific mutation influences the genetic make-up of glioma and the resulting prognosis. Key differences in co-mutation and gene expression levels were identified that correlate with an improved prognosis. Gliomas are differentiated into two major disease subtypes, astrocytoma or oligodendroglioma, which are then characterized as either IDH (isocitrate dehydrogenase)-wild type or IDH-mutant due to the dramatic differences in prognosis and overall survival. Here, we investigated the genetic background of IDH1-mutant gliomas using the Catalogue of Somatic Mutations in Cancer (COSMIC) database. In astrocytoma patients, we found that IDH1 is often co-mutated with TP53, ATRX, AMBRA1, PREX1, and NOTCH1, but not CHEK2, EGFR, PTEN, or the zinc finger transcription factor ZNF429. The majority of the mutations observed in these genes were further confirmed to be either drivers or pathogenic by the Cancer-Related Analysis of Variants Toolkit (CRAVAT). Gene expression analysis showed down-regulation of DRG2 and MSN expression, both of which promote cell proliferation and invasion. There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btt017
发表时间：
2013-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Douville C;Carter H;Kim R;Niknafs N;Diekhans M;Stenson PD;Cooper DN;Ryan M;Karchin R
通讯作者：
Karchin R
影响因子：
64.8
作者：
通讯作者：
--
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
3.8
作者：
Barbirou M;Woldu HG;Sghaier I;Bedoui SA;Mokrani A;Aami R;Mezlini A;Yacoubi-Loueslati B;Tonellato PJ;Bouhaouala-Zahar B
通讯作者：
Bouhaouala-Zahar B
影响因子：
16.6
作者：
Carbonneau, Melissa;Gagne, Laurence M.;Lalonde, Marie-Eve;Germain, Marie-Anne;Motorina, Alena;Guiot, Marie-Christine;Secco, Blandine;Vincent, Emma E.;Tumber, Anthony;Hulea, Laura;Bergeman, Jonathan;Oppermann, Udo;Jones, Russell G.;Laplante, Mathieu;Topisirovic, Ivan;Petrecca, Kevin;Huot, Marc-Etienne;Mallette, Frederick A.
通讯作者：
Mallette, Frederick A.