Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors.

IF 11.1 Q1 CELL BIOLOGY
Cell genomics Pub Date : 2024-11-13 Epub Date: 2024-10-14 DOI:10.1016/j.xgen.2024.100675
Ianthe A E M van Belzen, Marc van Tuil, Shashi Badloe, Alex Janse, Eugène T P Verwiel, Marcel Santoso, Sam de Vos, John Baker-Hernandez, Hindrik H D Kerstens, Nienke Solleveld-Westerink, Michael T Meister, Jarno Drost, Marry M van den Heuvel-Eibrink, Johannes H M Merks, Jan J Molenaar, Weng Chuan Peng, Bastiaan B J Tops, Frank C P Holstege, Patrick Kemmeren, Jayne Y Hehir-Kwa
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引用次数: 0

Abstract

In pediatric cancer, structural variants (SVs) and copy-number alterations contribute to cancer initiation as well as progression, thereby aiding diagnosis and treatment stratification. Although suggested to be of importance, the prevalence and biological relevance of complex genomic rearrangements (CGRs) across pediatric solid tumors is largely unexplored. In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy, and chromothripsis across five pediatric solid cancer types. CGRs were identified in 56 tumors (47%), and in 42 of these tumors, CGRs affect cancer driver genes or result in unfavorable chromosomal alterations. This demonstrates that CGRs are prevalent and pathogenic in pediatric solid tumors and suggests that selection likely contributes to the structural variation landscape. Moreover, carrying CGRs is associated with more adverse clinical events. Our study highlights the potential for CGRs to be incorporated in risk stratification or exploited for targeted treatments.

复杂的结构变异在小儿实体瘤中非常普遍,而且致病性很强。
在小儿癌症中,结构变异(SV)和拷贝数改变有助于癌症的发生和发展,从而有助于诊断和治疗分层。虽然复杂基因组重排(CGRs)在儿科实体瘤中被认为非常重要,但其发生率和生物学相关性在很大程度上仍未得到探讨。在一组 120 例原发性肿瘤中,我们系统地描述了五种儿科实体瘤中染色体外 DNA、染色体畸变和染色体三倍体的模式。在 56 个肿瘤(47%)中发现了 CGRs,其中 42 个肿瘤的 CGRs 影响了癌症驱动基因或导致了不利的染色体改变。这表明CGRs在小儿实体瘤中普遍存在并具有致病性,同时也表明选择很可能是结构变异的原因之一。此外,携带 CGRs 与更多不良临床事件有关。我们的研究强调了CGRs被纳入风险分层或用于靶向治疗的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
7.10
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