圣犹达儿童研究医院Jinghui Zhang小组取得一项新突破。他们的研究开发出了儿童癌症结构变异全景。这一研究成果发表在2026年3月12日出版的国际学术期刊《癌细胞》上。

结构变异（SVs）占儿童癌症驱动变异的60%以上。对1616名儿童和2203名成人全基因组的泛癌症分析显示，儿童SV负担在不同癌症类型之间差异约100倍，与成人脑瘤和实体瘤相比减少了6- 16倍，但在血液恶性肿瘤中是相当的。排名靠前的SV破坏基因是儿童癌症和成人癌症脆弱部位的驱动因素。

在儿童急性淋巴细胞白血病中，靠近RAG重组信号序列的复发性SV热点会破坏免疫基因座和驱动基因，但在成人淋巴细胞癌中却只会破坏免疫基因座。10个提取的SV特征表明，RAG介导的突变是淋巴细胞癌中COSMIC SV7的潜在病因，而对13例患者的时空不同样本进行测序，揭示了SV对肿瘤内异质性和驱动因子选择的持续进化贡献。他们的研究扩大了RAG介导的突变的已知范围，而整理的SV数据集可以指导未来的研究和临床试验。

附：英文原文

Title: The landscape of structural variation in pediatric cancer

Author: Robert Greenhalgh, Samuel W. Brady, Wentao Yang, Diane A. Flasch, Michael N. Edmonson, Nadezhda V. Terekhanova, Yanling Liu, Jian Wang, Karol A. Szlachta, Liqing Tian, Daniel K. Putnam, Delaram Rahbarinia, Pandurang Kolekar, Xin Zhou, Daniela S. Gerhard, Xiaotu Ma, Jinghui Zhang

Issue&Volume: 2026-03-12

Abstract: Structural variants (SVs) account for over 60% of pediatric cancer driver variants. Pan-cancer analyses on 1,616 pediatric and 2,203 adult whole genomes show that pediatric SV burden varies ～100-fold across cancer types, is reduced 6- to 16-fold compared to adult brain and solid tumors, but is comparable in hematological malignancies. The top-ranked SV-disrupted genes are drivers in pediatric cancers and fragile sites in adult cancers. Recurrent SV hotspots near RAG recombination signal sequences disrupt immune loci and driver genes in pediatric acute lymphoblastic leukemias, but immune loci exclusively in adult lymphoid cancers. Ten extracted SV signatures implicate RAG-mediated mutagenesis as a potential etiology for COSMIC SV7 in lymphoid cancers, while clustering of spatiotemporally distinct samples from 13 patients reveals the ongoing evolutionary contributions of SVs to intra-tumor heterogeneity and driver selection. Our study expands the known scope of RAG-mediated mutagenesis, while the curated SV dataset can guide future research and clinical testing.

DOI: 10.1016/j.ccell.2026.02.012

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(26)00110-8