Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-01-17 DOI:10.1016/j.isci.2024.111510

Yuchen Zeng (曾雨晨) , Wei Lv (吕伟) , Huiying Tao (陶荟颖) , Conghui Li (李聪慧) , Shiqi Jiang (蒋世琪) , Yuan Liang (梁媛) , Chen Chen (陈晨) , Tianxi Yu (于天熙) , Yue Li (李悦) , Shuang Wu (吴双) , Xin Cui (崔鑫) , Ning Liang (梁宁) , Ping Wang (王平) , Huixin Xu (许荟馨) , Jingjing Dong (董晶晶) , Huajing Teng (滕花景) , Ke Chen (谌科) , Kai Mu (穆锴) , Tianda Fan (范天达) , Xiaoping Cen (岑萧萍) , Peng Han (韩鹏)

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引用次数: 0

Abstract

Chromothripsis, a hallmark of cancer, is characterized by extensive and localized DNA rearrangements involving one or a few chromosomes. However, its genome-wide frequency and characteristics in urothelial carcinoma (UC) remain largely unknown. Here, by analyzing single-regional and multi-regional whole-genome sequencing (WGS), we present the chromothripsis blueprint in 488 UC patients. Chromothripsis events exhibit significant intertumoral heterogeneity, being detected in 41% of UC patients, with an increase from 30% in non-muscle-invasive disease (Ta/1) to 53% in muscle-invasive disease (T2-4). The presence of chromothripsis correlates with an unstable cancer genome and poor clinical outcomes. Analysis of multi-regional WGS data from 52 patients revealed pronounced intratumoral heterogeneity with chromothripsis events detectable only in specific tumor regions rather than uniformly across all areas. Chromothripsis events evolve under positive selection and contribute to tumor dissemination. This study presents a comprehensive genome-wide chromothripsis landscape in UC, highlighting the significance of chromothripsis in UC development.

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绘制尿路上皮癌的染色体分裂景观揭示了肿瘤内和肿瘤间的巨大异质性。

染色体断裂是癌症的一个标志，其特征是涉及一条或几条染色体的广泛和局部DNA重排。然而，其在尿路上皮癌（UC）中的全基因组频率和特征在很大程度上仍然未知。在这里，通过分析单区域和多区域全基因组测序（WGS），我们提出了488例UC患者的染色体剥离蓝图。染色体剥离事件表现出明显的肿瘤间异质性，在41%的UC患者中检测到，从非肌肉侵袭性疾病的30% （Ta/1）增加到肌肉侵袭性疾病的53% （T2-4）。染色体断裂的存在与不稳定的癌症基因组和不良的临床结果相关。来自52例患者的多区域WGS数据分析显示，仅在特定肿瘤区域可检测到染色体碎裂事件，而不是在所有区域均可检测到。染色体裂解事件在正选择下进化并促进肿瘤扩散。本研究介绍了UC中全基因组的染色体裂解情况，强调了染色体裂解在UC发展中的意义。

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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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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