非典型畸胎样/横纹肌样肿瘤由三个具有不同增强子景观的表观遗传亚群组成。
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
机构信息
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany; German Cancer Consortium (DKTK), Core Center Heidelberg, 69120 Heidelberg, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany; German Cancer Consortium (DKTK), Core Center Heidelberg, 69120 Heidelberg, Germany; European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany.
出版信息
Cancer Cell. 2016 Mar 14;29(3):379-393. doi: 10.1016/j.ccell.2016.02.001. Epub 2016 Feb 25.
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
胚胎发育不良性神经外胚层肿瘤（ATRT）是婴儿中最常见的脑肿瘤之一。尽管 ATRT 患者的预后较差，但部分患者对现有治疗方法反应良好，提示肿瘤间存在分子异质性。为了进一步研究这一问题，我们对 192 例 ATRT 进行了遗传和表观遗传分析。发现 ATRT 存在三个不同的分子亚群，与人口统计学、肿瘤位置和 SMARCB1 改变类型的差异相关。全基因组 DNA 和 RNA 测序除了发现 SMARCB1 之外，没有发现其他能够解释亚群间差异的高频突变。然而，对原发性肿瘤的全基因组亚硫酸氢盐测序和 H3K27Ac 染色质免疫沉淀测序揭示了明显的差异，导致了亚群特异性调控网络和潜在治疗靶点的鉴定。
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