Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes
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DOI：
10.1016/j.ccell.2016.02.001
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发表时间：
2016-03-14
期刊：
影响因子：
50.3
通讯作者：
Kool, Marcel
中科院分区：
文献类型：
--
作者：
Johann, Pascal D.;Erkek, Serap;Kool, Marcel
非典型的霉菌/色肽肿瘤（ATRT）是婴儿最常见的脑肿瘤之一。尽管ATRT患者的预后较差，但一些患者对当前治疗的反应表明，表明分子间肿瘤异质性。为了进一步研究，我们在遗传和表观遗传上分析了192个ATRT。鉴定出与人口统计学，肿瘤位置和SMARCB1改变类型有关的三个不同的ATRT分子亚组。全基因组DNA和RNA测序发现除了SMARCB1之外，没有复发突变，可以解释亚组之间的差异。然而，全基因组亚硫酸氢盐测序和H3K27AC染色质 - 免疫沉淀测序对原发性肿瘤进行了明显差异，从而鉴定了亚组特异性调节网络和潜在的治疗靶标。
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.