低突变型肾母细胞瘤的高分辨率克隆结构

High resolution clonal architecture of hypomutated Wilms tumours.

作者信息

Lee-Six Henry, Treger Taryn D, Dave Manas, Coorens Tim Hh, Anderson Nathaniel D, Tiersma Yvonne, Derakhshan Sepide, de Haan Sanne, van den Heuvel-Eibrink Marry M, Wang Yichen, Wenger Anna, Al-Saadi Reem, Lawford Alice, Letunovska Aleksandra, Wegert Jenny, Parks Conor, Morcrette Guillaume, Gessler Manfred, Vujanic Gordan, Chowdhury Tanzina, J O'Sullivan Maureen, de Krijger Ronald R, Stratton Michael R, Pritchard-Jones Kathy, Hutchinson J Ciaran, Drost Jarno, Behjati Sam

机构信息

Wellcome Sanger Institute, Hinxton, UK.

Department of Pathology, University of Cambridge, Cambridge, UK.

出版信息

Nat Commun. 2025 May 29;16(1):4647. doi: 10.1038/s41467-025-59854-4.

DOI:10.1038/s41467-025-59854-4

PMID:40442086

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12122882/

Abstract

A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We find that apparent hypomutation is the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged.

摘要

儿童癌症的一个范例是它们的突变负担较低，有些表面上的突变比其来源的正常组织还要少。我们着手通过使用高分辨率、高深度测序方法研究具有极少突变的儿科肾癌来解决这一矛盾。我们发现，明显的低突变是肿瘤进化的正常组织样模式导致的异常克隆结构的结果，这增加了一些癌症的突变负担被系统性误判的可能性。