Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V7Z 1L3, Canada.
Hopp Children's Cancer Center, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg, Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Cell Rep. 2019 Nov 19;29(8):2338-2354.e7. doi: 10.1016/j.celrep.2019.10.013. Epub 2019 Nov 7.
Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features. We identify five DNA methylation subgroups associated with anatomical sites and SMARCB1 mutation patterns. Groups 1, 3, and 4 exhibit cytotoxic T cell infiltration and expression of immune checkpoint regulators, consistent with a potential role for immunotherapy in rhabdoid tumor patients.
颅外恶性横纹肌样肿瘤（MRTs）和颅内非典型畸胎瘤样横纹肌样肿瘤（ATRTs）是主要由 SMARCB1 缺失驱动的异质性儿科癌症。为了了解 MRTs 和 ATRTs 之间全基因组分子关系，我们分析了 140 例 MRTs 和 161 例 ATRTs 的多组学数据。我们发现 ATRT-MYC 亚组（ATRT-MYC）与颅外 MRTs 之间存在相似性，包括全局 DNA 低甲基化以及 HOX 基因和参与间充质发育的基因的过表达，这将它们与表达神经样特征的其他 ATRT 亚组区分开来。我们确定了与解剖部位和 SMARCB1 突变模式相关的五个 DNA 甲基化亚组。第 1、3 和 4 组表现出细胞毒性 T 细胞浸润和免疫检查点调节剂的表达，这与横纹肌样肿瘤患者免疫治疗的潜在作用一致。
