INSERM, U830, Pediatric Translational Research, PSL Research University, Institut Curie, Paris, France.
INSERM, U900, Paris, France.
J Pathol. 2021 Sep;255(1):1-15. doi: 10.1002/path.5705. Epub 2021 Jun 23.
Extracranial rhabdoid tumours (ECRTs) are an aggressive malignancy of infancy and early childhood. The vast majority of cases demonstrate inactivation of SMARCB1 (ECRT ) on a background of a remarkably stable genome, a low mutational burden, and no other recurrent mutations. Rarely, ECRTs can harbour the alternative inactivation of SMARCA4 (ECRT ) instead of SMARCB1. However, very few ECRT cases have been published to date, and a systematic characterization of ECRT is missing from the literature. In this study, we report the clinical, pathological, and genomic features of additional cases of ECRT and show that they are comparable to those of ECRT We also assess whether ECRT , ECRT , and small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT) represent distinct or overlapping entities at a molecular level. Using DNA methylation and transcriptomics-based tumour classification approaches, we demonstrate that ECRT display molecular features intermediate between SCCOHT and ECRT ; however, ECRT appear to be more closely related to SCCOHT by DNA methylation. Conversely, both transcriptomics and DNA methylation show a larger gap between SCCOHT and ECRT , potentially supporting their continuous separate classification. Lastly, we show that ECRT display concomitant lack of SMARCA4 (BRG1) and SMARCA2 (BRM) expression at the protein level, similar to what is seen in SCCOHT. Overall, these results expand our knowledge on this rare tumour type and explore the similarities and differences among entities from the 'rhabdoid tumour' spectrum. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
颅外横纹肌样肿瘤(ECRTs)是婴儿和幼儿期具有侵袭性的恶性肿瘤。绝大多数病例表现为 SMARCB1(ECRT)失活,同时具有显著稳定的基因组、低突变负担和其他非反复突变。极少数情况下,ECRT 可能具有替代性的 SMARCA4(ECRT)失活,而不是 SMARCB1。然而,迄今为止,发表的 ECRT 病例很少,文献中也缺乏对 ECRT 的系统描述。在本研究中,我们报告了额外 ECRT 病例的临床、病理和基因组特征,并表明它们与 ECRT 相似。我们还评估了 ECRT、ECRT 和卵巢小细胞癌伴高钙血症型(SCCOHT)在分子水平上是否代表不同或重叠的实体。使用基于 DNA 甲基化和转录组学的肿瘤分类方法,我们证明 ECRT 显示出介于 SCCOHT 和 ECRT 之间的分子特征;然而,通过 DNA 甲基化,ECRT 似乎与 SCCOHT 更为密切相关。相反,转录组学和 DNA 甲基化都显示出 SCCOHT 和 ECRT 之间更大的差距,这可能支持它们的连续单独分类。最后,我们表明 ECRT 显示出同时缺乏 SMARCA4(BRG1)和 SMARCA2(BRM)的蛋白表达,这与 SCCOHT 中所见相似。总之,这些结果扩展了我们对这种罕见肿瘤类型的认识,并探讨了“横纹肌瘤”谱中实体之间的异同。