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

Yuchen Zeng; Wei Lv; Huiying Tao; Conghui Li; Shiqi Jiang; Yuan Liang; Chen Chen; Tianxi Yu; Yue Li; Shuang Wu; Xin Cui; Ning Liang; Ping Wang; Huixin Xu; Jingjing Dong; Huajing Teng; Ke Chen; Kai Mu; Tianda Fan; Xiaoping Cen; Zhe Xu; Ming Zhu; Wenting Wang; Jia Mi; Xi Xiang; Wei Dong; Huanming Yang; Lars Bolund; Lin Lin; Jinzhao Song; Xicheng Song; Yonglun Luo; Chunhua Lin; Peng Han

doi:10.1016/j.isci.2024.111510

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

Yuchen Zeng
, Wei Lv
, Huiying Tao
, Conghui Li
, Shiqi Jiang
, Yuan Liang
, Chen Chen
, Tianxi Yu
, Yue Li
, Shuang Wu
, Xin Cui
, Ning Liang
, Ping Wang
, Huixin Xu
, Jingjing Dong
, Huajing Teng
, Ke Chen
, Kai Mu
, Tianda Fan
, Xiaoping Cen

Zhe Xu, Ming Zhu, Wenting Wang, Jia Mi, Xi Xiang, Wei Dong, Huanming Yang, Lars Bolund, Lin Lin, Jinzhao Song, Xicheng Song, Yonglun Luo, Chunhua Lin, Peng Han

Department of Biomedicine - Forskning og uddannelse, Skou-bygningen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	111510
Journal	iScience
Volume	28
Issue	1
Pages (from-to)	111510
ISSN	2589-0042
DOIs	https://doi.org/10.1016/j.isci.2024.111510
Publication status	Published - 17 Jan 2025

Keywords

Cancer
Cancer systems biology
Genomic analysis
Genomics

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10.1016/j.isci.2024.111510

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Zeng, Y., Lv, W., Tao, H., Li, C., Jiang, S., Liang, Y., Chen, C., Yu, T., Li, Y., Wu, S., Cui, X., Liang, N., Wang, P., Xu, H., Dong, J., Teng, H., Chen, K., Mu, K., Fan, T., ... Han, P. (2025). Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity. iScience, 28(1), 111510. Article 111510. https://doi.org/10.1016/j.isci.2024.111510

@article{21a2e30143e9489a871d0dc5883782e2,

title = "Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity",

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.",

keywords = "Cancer, Cancer systems biology, Genomic analysis, Genomics",

author = "Yuchen Zeng and Wei Lv and Huiying Tao and Conghui Li and Shiqi Jiang and Yuan Liang and Chen Chen and Tianxi Yu and Yue Li and Shuang Wu and Xin Cui and Ning Liang and Ping Wang and Huixin Xu and Jingjing Dong and Huajing Teng and Ke Chen and Kai Mu and Tianda Fan and Xiaoping Cen and Zhe Xu and Ming Zhu and Wenting Wang and Jia Mi and Xi Xiang and Wei Dong and Huanming Yang and Lars Bolund and Lin Lin and Jinzhao Song and Xicheng Song and Yonglun Luo and Chunhua Lin and Peng Han",

note = "{\textcopyright} 2024 The Author(s).",

year = "2025",

month = jan,

day = "17",

doi = "10.1016/j.isci.2024.111510",

language = "English",

volume = "28",

pages = "111510",

journal = "iScience",

issn = "2589-0042",

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}

Zeng, Y, Lv, W, Tao, H, Li, C, Jiang, S, Liang, Y, Chen, C, Yu, T, Li, Y, Wu, S, Cui, X, Liang, N, Wang, P, Xu, H, Dong, J, Teng, H, Chen, K, Mu, K, Fan, T, Cen, X, Xu, Z, Zhu, M, Wang, W, Mi, J, Xiang, X, Dong, W, Yang, H, Bolund, L, Lin, L, Song, J, Song, X, Luo, Y, Lin, C & Han, P 2025, 'Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity', iScience, vol. 28, no. 1, 111510, pp. 111510. https://doi.org/10.1016/j.isci.2024.111510

Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity. / Zeng, Yuchen; Lv, Wei; Tao, Huiying et al.
In: iScience, Vol. 28, No. 1, 111510, 17.01.2025, p. 111510.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Mapping the chromothripsis landscape in urothelial carcinoma unravels great intratumoral and intertumoral heterogeneity

AU - Zeng, Yuchen

AU - Lv, Wei

AU - Tao, Huiying

AU - Li, Conghui

AU - Jiang, Shiqi

AU - Liang, Yuan

AU - Chen, Chen

AU - Yu, Tianxi

AU - Li, Yue

AU - Wu, Shuang

AU - Cui, Xin

AU - Liang, Ning

AU - Wang, Ping

AU - Xu, Huixin

AU - Dong, Jingjing

AU - Teng, Huajing

AU - Chen, Ke

AU - Mu, Kai

AU - Fan, Tianda

AU - Cen, Xiaoping

AU - Xu, Zhe

AU - Zhu, Ming

AU - Wang, Wenting

AU - Mi, Jia

AU - Xiang, Xi

AU - Dong, Wei

AU - Yang, Huanming

AU - Bolund, Lars

AU - Lin, Lin

AU - Song, Jinzhao

AU - Song, Xicheng

AU - Luo, Yonglun

AU - Lin, Chunhua

AU - Han, Peng

PY - 2025/1/17

Y1 - 2025/1/17

N2 - 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.

AB - 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.

KW - Cancer

KW - Cancer systems biology

KW - Genomic analysis

KW - Genomics

UR - https://www.scopus.com/pages/publications/85211999630

U2 - 10.1016/j.isci.2024.111510

DO - 10.1016/j.isci.2024.111510

M3 - Journal article

C2 - 39790556

SN - 2589-0042

VL - 28

SP - 111510

JO - iScience

JF - iScience

IS - 1

M1 - 111510

ER -

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

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