No small surprise-small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour
No small surprise-small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour
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DOI：
10.1002/path.4362
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发表时间：
2014-07-01
影响因子：
7.3
通讯作者：
McCluggage, W. Glenn
中科院分区：
文献类型：
--
作者：
Foulkes, William D.;Clarke, Blaise A.;McCluggage, W. Glenn
全外显子组测序（WES）正在彻底改变医学诊断和分类学。自首次使用以来不到5年，WES已经揭示了许多癌症的意想不到的分子驱动因素。在这里，我们描述了我们使用WES来揭示一个神秘的病理实体的真实性质，卵巢小细胞癌，高钙血症型（SCCOHT），它一直抵制明确的特征，因为它是在1979年首次描述。我们使用三个SCCOHT家族进行了WES，并在所有病例中鉴定了染色质重塑基因SMARCA 4（编码BRG 1）的有害突变。对这些发现的后续研究，使用福尔马林固定石蜡包埋肿瘤的桑格测序和WES，表明几乎所有我们研究的SCCOHT都缺乏功能性SMARCA 4/BRG 1。值得注意的是，该基因和相关的SMARCB 1基因在大多数（如果不是全部）非典型畸胎瘤/横纹肌样肿瘤和恶性横纹肌样肿瘤中发生突变。其他团体也有类似的发现。我们回顾这三种肿瘤之间的关系，讨论它们是如何从形态学上相似的肿瘤区分，考虑它们的相似性，并显示如何WES揭示SCCOHTs实际上是横纹肌样肿瘤。我们建议将SCCOHT重新命名为卵巢恶性横纹肌样瘤（MRTO）以反映这些观察结果。版权所有（c）2014大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Whole-exome sequencing (WES) is revolutionizing medical diagnostics and taxonomy. In less than 5 years since its first use, WES has revealed unexpected molecular drivers of numerous cancers. Here, we describe our use of WES to uncover the true nature of an enigmatic pathological entity, small-cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), which has resisted definitive characterisation since it was first described in 1979. We conducted WES using three families with SCCOHT and identified deleterious mutations in the chromatin-remodelling gene SMARCA4 (encoding BRG1) in all cases. Follow-up of these findings, using both Sanger sequencing and WES of formalin-fixed paraffin-embedded tumours, showed that virtually all SCCOHTs we studied lacked functional SMARCA4/BRG1. Notably, this gene, and the related SMARCB1 gene, is mutated in most, if not all, atypical teratoid/rhabdoid tumours and malignant rhabdoid tumours. Other groups have similar findings. We review the relationship between these three neoplasms, discuss how they were distinguished from morphologically similar neoplasms, consider their similarities and show how WES has revealed that SCCOHTs are in fact rhabdoid tumours. We propose that SCCOHT be renamed malignant rhabdoid tumour of the ovary' (MRTO) to reflect these observations. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.