Chromatin structure predicts survival in glioma patients.
Chromatin structure predicts survival in glioma patients.
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染色质结构可预测胶质瘤患者的存活率。
DOI：
10.1038/s41598-022-11019-9
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发表时间：
2022-05-17
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
表观遗传学和基因调控的病理变化，伴随着低级别到高级别胶质瘤的进展是研究不足。作者使用来自手术切除的胶质瘤标本的大量配对atac-seq和RNA-seq数据来推断胶质瘤中的基因调控关系。38个神经胶质瘤患者样本进行atac-seq测序，16个样本进行额外的RNA-seq分析。使用atac-seq/RNA-seq相关矩阵，atac-seq峰与基于高相关值的基因配对（|R2|> 0.6）。样本按IDH 1状态聚类，但不按等级聚类。令人惊讶的是，IDH 1突变体样品有具有更多峰的趋势。大多数峰与存活率正相关，与基因表达正相关。构建前六个atac-seq峰的模型创建了高度准确的存活预测模型（r2 = 0.68）。在控制了年龄、分级、病理、IDH 1状态和性别后，这些峰中的四个仍然是显著的。II级、III级和IV级（主要）样本具有相似的转录因子和基因模块。然而，IV级（复发性）样本的峰值非常少。患者来源的神经胶质瘤培养物显示辐射后峰值计数减少，表明这可能是辐射诱导的。这项研究支持IDH 1突变型和IDH 1野生型胶质瘤具有不同的表观遗传景观的观点，并且由atac-seq峰映射的可访问染色质位点往往与表达呈正相关。这项研究中的数据导致了一种新的治疗反应模型，其中胶质瘤细胞通过关闭DNA的开放区域对放射治疗作出反应。
The pathological changes in epigenetics and gene regulation that accompany the progression of low-grade to high-grade gliomas are under-studied. The authors use a large set of paired atac-seq and RNA-seq data from surgically resected glioma specimens to infer gene regulatory relationships in glioma. Thirty-eight glioma patient samples underwent atac-seq sequencing and 16 samples underwent additional RNA-seq analysis. Using an atac-seq/RNA-seq correlation matrix, atac-seq peaks were paired with genes based on high correlation values (|r2| > 0.6). Samples clustered by IDH1 status but not by grade. Surprisingly there was a trend for IDH1 mutant samples to have more peaks. The majority of peaks are positively correlated with survival and positively correlated with gene expression. Constructing a model of the top six atac-seq peaks created a highly accurate survival prediction model (r2 = 0.68). Four of these peaks were still significant after controlling for age, grade, pathology, IDH1 status and gender. Grade II, III, and IV (primary) samples have similar transcription factors and gene modules. However, grade IV (recurrent) samples have strikingly few peaks. Patient-derived glioma cultures showed decreased peak counts following radiation indicating that this may be radiation-induced. This study supports the notion that IDH1 mutant and IDH1 wildtype gliomas have different epigenetic landscapes and that accessible chromatin sites mapped by atac-seq peaks tend to be positively correlated with expression. The data in this study leads to a new model of treatment response wherein glioma cells respond to radiation therapy by closing open regions of DNA.
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DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
DOI：
10.22088/ijmcm.bums.8.2.103
发表时间：
2019-01-01
影响因子：
--
作者：
Khorasani, Maryam;Shahbazi, Shirin;Mahdian, Reza
通讯作者：
Mahdian, Reza
影响因子：
48
作者：
Habib N;Avraham-Davidi I;Basu A;Burks T;Shekhar K;Hofree M;Choudhury SR;Aguet F;Gelfand E;Ardlie K;Weitz DA;Rozenblatt-Rosen O;Zhang F;Regev A
通讯作者：
Regev A
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.