Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation.
Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation.
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DOI：
10.1186/s12885-021-09077-9
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发表时间：
2021-12-18
期刊：
影响因子：
3.8
通讯作者：
Murphy PJ
中科院分区：
文献类型：
--
作者：
Ruff GL;Murphy KE;Smith ZR;Vertino PM;Murphy PJ
染色质状态为维持转录模式提供了清晰可解读的蓝图，举例说明了分裂细胞中有丝分裂稳定的细胞编程形式。在这方面，对癌组织中染色质状态的基因组研究有可能揭示肿瘤生物学的新方面以及与疾病表型和结果相关的独特机制。染色质状态差异在多大程度上与乳腺癌的特征相一致还没有确定。我们应用了一系列无监督的计算方法来识别人类乳腺癌肿瘤中与离散生理相关的染色质和分子差异。单独的染色质模式能够将肿瘤与癌症亚型和疾病进展相关联。在激素受体阳性肿瘤中，转录因子FOXA1的DNA基序和基底样肿瘤中SOX9的DNA基序存在主要差异。我们发现这种效应的一个潜在驱动因素是组蛋白伴侣ANP32E，它与肿瘤进展和FOXA1结合位点染色质松弛呈负相关。具有高水平ANP32E的肿瘤表现出免疫应答和增殖基因表达特征，而具有低水平ANP32E的肿瘤则表现出分化程序。我们的研究结果表明，ANP32E可能通过染色质状态调节来控制乳腺癌的分化和肿瘤的可塑性。这项研究为未来在癌变过程中染色质变化的计算研究开创了先例。在线版本包含补充材料，可在10.1186/s12885-021-09077-9获得。
Chromatin state provides a clear decipherable blueprint for maintenance of transcriptional patterns, exemplifying a mitotically stable form of cellular programming in dividing cells. In this regard, genomic studies of chromatin states within cancerous tissues have the potential to uncover novel aspects of tumor biology and unique mechanisms associated with disease phenotypes and outcomes. The degree to which chromatin state differences occur in accordance with breast cancer features has not been established. We applied a series of unsupervised computational methods to identify chromatin and molecular differences associated with discrete physiologies across human breast cancer tumors. Chromatin patterns alone are capable of stratifying tumors in association with cancer subtype and disease progression. Major differences occur at DNA motifs for the transcription factor FOXA1, in hormone receptor-positive tumors, and motifs for SOX9 in Basal-like tumors. We find that one potential driver of this effect, the histone chaperone ANP32E, is inversely correlated with tumor progression and relaxation of chromatin at FOXA1 binding sites. Tumors with high levels of ANP32E exhibit an immune response and proliferative gene expression signature, whereas tumors with low ANP32E levels appear programmed for differentiation. Our results indicate that ANP32E may function through chromatin state regulation to control breast cancer differentiation and tumor plasticity. This study sets a precedent for future computational studies of chromatin changes in carcinogenesis. The online version contains supplementary material available at 10.1186/s12885-021-09077-9.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
实现癌症基因组数据的共同愿景。
DOI：
10.1056/nejmp1607591
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grossman RL;Heath AP;Ferretti V;Varmus HE;Lowy DR;Kibbe WA;Staudt LM
通讯作者：
Staudt LM
影响因子：
10.5
作者：
Gevry, Nicolas;Hardy, Sara;Gaudreau, Luc
通讯作者：
Gaudreau, Luc
影响因子：
2.7
作者：
Cai, Wesley L.;Greer, Celeste B.;Nguyen, Don X.
通讯作者：
Nguyen, Don X.
影响因子：
14.9
作者：
Brunelle M;Nordell Markovits A;Rodrigue S;Lupien M;Jacques PÉ;Gévry N
通讯作者：
Gévry N