Ongoing genome doubling shapes evolvability and immunity in ovarian cancer
Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis1-6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing,...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
16 July 2025
|
| In: |
Nature
Year: 2025, Jahrgang: 644, Heft: 8078, Pages: 1078-1087, [1-29] |
| ISSN: | 1476-4687 |
| DOI: | 10.1038/s41586-025-09240-3 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41586-025-09240-3 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41586-025-09240-3 
|
| Verfasserangaben: | Andrew McPherson, Ignacio Vázquez-García, Matthew A. Myers, Duaa H. Al-Rawi, Matthew Zatzman, Adam C. Weiner, Samuel Freeman, Neeman Mohibullah, Gryte Satas, Marc J. Williams, Nicholas Ceglia, Danguolė Norkūnaitė, Allen W. Zhang, Jun Li, Jamie L.P. Lim, Michelle Wu, Seongmin Choi, Eliyahu Havasov, Diljot Grewal, Hongyu Shi, Minsoo Kim, Roland F. Schwarz, Tom Kaufmann, Khanh Ngoc Dinh, Florian Uhlitz, Julie Tran, Yushi Wu, Ruchi Patel, Satish Ramakrishnan, DooA Kim, Justin Clarke, Hunter Green, Emily Ali, Melody DiBona, Nancy Varice, Ritika Kundra, Vance Broach, Ginger J. Gardner, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Sarah H. Kim, Rachel N. Grisham, Ying L. Liu, Agnes Viale, Nicole Rusk, Yulia Lakhman, Lora H. Ellenson, Simon Tavaré, Samuel Aparicio, Dennis S. Chi, Carol Aghajanian, Nadeem R. Abu-Rustum, Claire F. Friedman, Dmitriy Zamarin, Britta Weigelt, Samuel F. Bakhoum & Sohrab P. Shah |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1942961596 | ||
| 003 | DE-627 | ||
| 005 | 20251201114014.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 251201s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41586-025-09240-3 |2 doi | |
| 035 | |a (DE-627)1942961596 | ||
| 035 | |a (DE-599)KXP1942961596 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a McPherson, Andrew |e VerfasserIn |0 (DE-588)1383118779 |0 (DE-627)1943014795 |4 aut | |
| 245 | 1 | 0 | |a Ongoing genome doubling shapes evolvability and immunity in ovarian cancer |c Andrew McPherson, Ignacio Vázquez-García, Matthew A. Myers, Duaa H. Al-Rawi, Matthew Zatzman, Adam C. Weiner, Samuel Freeman, Neeman Mohibullah, Gryte Satas, Marc J. Williams, Nicholas Ceglia, Danguolė Norkūnaitė, Allen W. Zhang, Jun Li, Jamie L.P. Lim, Michelle Wu, Seongmin Choi, Eliyahu Havasov, Diljot Grewal, Hongyu Shi, Minsoo Kim, Roland F. Schwarz, Tom Kaufmann, Khanh Ngoc Dinh, Florian Uhlitz, Julie Tran, Yushi Wu, Ruchi Patel, Satish Ramakrishnan, DooA Kim, Justin Clarke, Hunter Green, Emily Ali, Melody DiBona, Nancy Varice, Ritika Kundra, Vance Broach, Ginger J. Gardner, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Sarah H. Kim, Rachel N. Grisham, Ying L. Liu, Agnes Viale, Nicole Rusk, Yulia Lakhman, Lora H. Ellenson, Simon Tavaré, Samuel Aparicio, Dennis S. Chi, Carol Aghajanian, Nadeem R. Abu-Rustum, Claire F. Friedman, Dmitriy Zamarin, Britta Weigelt, Samuel F. Bakhoum & Sohrab P. Shah |
| 264 | 1 | |c 16 July 2025 | |
| 300 | |b Diagramme | ||
| 300 | |a 39 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 01.12.2025 | ||
| 520 | |a Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis1-6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process. WGD was associated with increased cell-cell diversity and higher rates of chromosomal missegregation and consequent micronucleation. We developed a mutation-based WGD timing method called doubleTime to delineate specific modes by which WGD can drive tumour evolution, including early fixation followed by considerable diversification, multiple parallel WGD events on a pre-existing background of copy-number diversity, and evolutionarily late WGD in small clones and individual cells. Furthermore, using matched single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signalling and cGAS-STING pathway activation result from ongoing chromosomal instability, but this is restricted to predominantly diploid tumours (WGD-low). By contrast, predominantly WGD tumours (WGD-high), despite increased missegregation, exhibited cell-cycle dysregulation, STING1 repression, and immunosuppressive phenotypic states. Together, these findings establish WGD as an ongoing mutational process that promotes evolvability and dysregulated immunity in high-grade serous ovarian cancer. | ||
| 650 | 4 | |a Cancer genomics | |
| 650 | 4 | |a Cancer microenvironment | |
| 650 | 4 | |a Phylogenetics | |
| 650 | 4 | |a Phylogeny | |
| 650 | 4 | |a Tumour heterogeneity | |
| 700 | 1 | |a Vázquez-García, Ignacio |e VerfasserIn |4 aut | |
| 700 | 1 | |a Myers, Matthew A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Al-Rawi, Duaa H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zatzman, Matthew |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weiner, Adam C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Freeman, Samuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mohibullah, Neeman |e VerfasserIn |4 aut | |
| 700 | 1 | |a Satas, Gryte |e VerfasserIn |4 aut | |
| 700 | 1 | |a Williams, Marc J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ceglia, Nicholas |e VerfasserIn |4 aut | |
| 700 | 1 | |a Norkūnaitė, Danguolė |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zhang, Allen W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Li, Jun |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lim, Jamie L. P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wu, Michelle |e VerfasserIn |4 aut | |
| 700 | 1 | |a Choi, Seongmin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Havasov, Eliyahu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Grewal, Diljot |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shi, Hongyu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kim, Minsoo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schwarz, Roland F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kaufmann, Tom |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dinh, Khanh Ngoc |e VerfasserIn |4 aut | |
| 700 | 1 | |a Uhlitz, Florian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tran, Julie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wu, Yushi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Patel, Ruchi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ramakrishnan, Satish |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kim, DooA |e VerfasserIn |4 aut | |
| 700 | 1 | |a Clarke, Justin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Green, Hunter |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ali, Emily |e VerfasserIn |4 aut | |
| 700 | 1 | |a DiBona, Melody |e VerfasserIn |4 aut | |
| 700 | 1 | |a Varice, Nancy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kundra, Ritika |e VerfasserIn |4 aut | |
| 700 | 1 | |a Broach, Vance |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gardner, Ginger J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roche, Kara Long |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sonoda, Yukio |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zivanovic, Oliver |d 1973- |e VerfasserIn |0 (DE-588)129602655 |0 (DE-627)474751309 |0 (DE-576)29774383X |4 aut | |
| 700 | 1 | |a Kim, Sarah H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Grisham, Rachel N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Liu, Ying L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Viale, Agnes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rusk, Nicole |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lakhman, Yulia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ellenson, Lora H. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tavaré, Simon |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aparicio, Samuel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chi, Dennis S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aghajanian, Carol |e VerfasserIn |4 aut | |
| 700 | 1 | |a Abu-Rustum, Nadeem R. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Friedman, Claire F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zamarin, Dmitriy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weigelt, Britta |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bakhoum, Samuel F. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shah, Sohrab P. |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature |d London [u.a.] : Nature Publ. Group, 1869 |g 644(2025), 8078, Seite 1078-1087, [1-29] |h Online-Ressource |w (DE-627)240151402 |w (DE-600)1413423-8 |w (DE-576)079718426 |x 1476-4687 |7 nnas |a Ongoing genome doubling shapes evolvability and immunity in ovarian cancer |
| 773 | 1 | 8 | |g volume:644 |g year:2025 |g number:8078 |g pages:1078-1087, [1-29] |g extent:39 |a Ongoing genome doubling shapes evolvability and immunity in ovarian cancer |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41586-025-09240-3 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41586-025-09240-3 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20251201 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 129602655 |a Zivanovic, Oliver |m 129602655:Zivanovic, Oliver |d 910000 |d 910400 |e 910000PZ129602655 |e 910400PZ129602655 |k 0/910000/ |k 1/910000/910400/ |p 41 | ||
| 999 | |a KXP-PPN1942961596 |e 4818127795 | ||
| BIB | |a Y | ||
| SER | |a newspaper | ||
| JSO | |a {"recId":"1942961596","language":["eng"],"note":["Gesehen am 01.12.2025"],"type":{"media":"Online-Ressource","bibl":"article-newspaper"},"title":[{"title_sort":"Ongoing genome doubling shapes evolvability and immunity in ovarian cancer","title":"Ongoing genome doubling shapes evolvability and immunity in ovarian cancer"}],"person":[{"display":"McPherson, Andrew","roleDisplay":"VerfasserIn","role":"aut","family":"McPherson","given":"Andrew"},{"role":"aut","display":"Vázquez-García, Ignacio","roleDisplay":"VerfasserIn","given":"Ignacio","family":"Vázquez-García"},{"given":"Matthew A.","family":"Myers","role":"aut","display":"Myers, Matthew A.","roleDisplay":"VerfasserIn"},{"display":"Al-Rawi, Duaa H.","roleDisplay":"VerfasserIn","role":"aut","family":"Al-Rawi","given":"Duaa H."},{"roleDisplay":"VerfasserIn","display":"Zatzman, Matthew","role":"aut","family":"Zatzman","given":"Matthew"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Weiner, Adam C.","given":"Adam C.","family":"Weiner"},{"family":"Freeman","given":"Samuel","roleDisplay":"VerfasserIn","display":"Freeman, Samuel","role":"aut"},{"given":"Neeman","family":"Mohibullah","role":"aut","roleDisplay":"VerfasserIn","display":"Mohibullah, Neeman"},{"display":"Satas, Gryte","roleDisplay":"VerfasserIn","role":"aut","family":"Satas","given":"Gryte"},{"family":"Williams","given":"Marc J.","roleDisplay":"VerfasserIn","display":"Williams, Marc J.","role":"aut"},{"family":"Ceglia","given":"Nicholas","display":"Ceglia, Nicholas","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Norkūnaitė","given":"Danguolė","display":"Norkūnaitė, Danguolė","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Zhang, Allen W.","role":"aut","family":"Zhang","given":"Allen W."},{"family":"Li","given":"Jun","display":"Li, Jun","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Lim, Jamie L. P.","role":"aut","family":"Lim","given":"Jamie L. P."},{"role":"aut","roleDisplay":"VerfasserIn","display":"Wu, Michelle","given":"Michelle","family":"Wu"},{"given":"Seongmin","family":"Choi","role":"aut","roleDisplay":"VerfasserIn","display":"Choi, Seongmin"},{"given":"Eliyahu","family":"Havasov","role":"aut","display":"Havasov, Eliyahu","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Grewal, Diljot","given":"Diljot","family":"Grewal"},{"roleDisplay":"VerfasserIn","display":"Shi, Hongyu","role":"aut","family":"Shi","given":"Hongyu"},{"given":"Minsoo","family":"Kim","role":"aut","display":"Kim, Minsoo","roleDisplay":"VerfasserIn"},{"family":"Schwarz","given":"Roland F.","display":"Schwarz, Roland F.","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Kaufmann, Tom","given":"Tom","family":"Kaufmann"},{"family":"Dinh","given":"Khanh Ngoc","display":"Dinh, Khanh Ngoc","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Florian","family":"Uhlitz","role":"aut","roleDisplay":"VerfasserIn","display":"Uhlitz, Florian"},{"given":"Julie","family":"Tran","role":"aut","display":"Tran, Julie","roleDisplay":"VerfasserIn"},{"role":"aut","display":"Wu, Yushi","roleDisplay":"VerfasserIn","given":"Yushi","family":"Wu"},{"family":"Patel","given":"Ruchi","roleDisplay":"VerfasserIn","display":"Patel, Ruchi","role":"aut"},{"display":"Ramakrishnan, Satish","roleDisplay":"VerfasserIn","role":"aut","family":"Ramakrishnan","given":"Satish"},{"role":"aut","display":"Kim, DooA","roleDisplay":"VerfasserIn","given":"DooA","family":"Kim"},{"display":"Clarke, Justin","roleDisplay":"VerfasserIn","role":"aut","family":"Clarke","given":"Justin"},{"given":"Hunter","family":"Green","role":"aut","display":"Green, Hunter","roleDisplay":"VerfasserIn"},{"role":"aut","display":"Ali, Emily","roleDisplay":"VerfasserIn","given":"Emily","family":"Ali"},{"role":"aut","display":"DiBona, Melody","roleDisplay":"VerfasserIn","given":"Melody","family":"DiBona"},{"display":"Varice, Nancy","roleDisplay":"VerfasserIn","role":"aut","family":"Varice","given":"Nancy"},{"role":"aut","display":"Kundra, Ritika","roleDisplay":"VerfasserIn","given":"Ritika","family":"Kundra"},{"family":"Broach","given":"Vance","roleDisplay":"VerfasserIn","display":"Broach, Vance","role":"aut"},{"given":"Ginger J.","family":"Gardner","role":"aut","display":"Gardner, Ginger J.","roleDisplay":"VerfasserIn"},{"family":"Roche","given":"Kara Long","roleDisplay":"VerfasserIn","display":"Roche, Kara Long","role":"aut"},{"given":"Yukio","family":"Sonoda","role":"aut","display":"Sonoda, Yukio","roleDisplay":"VerfasserIn"},{"role":"aut","display":"Zivanovic, Oliver","roleDisplay":"VerfasserIn","given":"Oliver","family":"Zivanovic"},{"role":"aut","display":"Kim, Sarah H.","roleDisplay":"VerfasserIn","given":"Sarah H.","family":"Kim"},{"family":"Grisham","given":"Rachel N.","roleDisplay":"VerfasserIn","display":"Grisham, Rachel N.","role":"aut"},{"display":"Liu, Ying L.","roleDisplay":"VerfasserIn","role":"aut","family":"Liu","given":"Ying L."},{"roleDisplay":"VerfasserIn","display":"Viale, Agnes","role":"aut","family":"Viale","given":"Agnes"},{"role":"aut","display":"Rusk, Nicole","roleDisplay":"VerfasserIn","given":"Nicole","family":"Rusk"},{"given":"Yulia","family":"Lakhman","role":"aut","display":"Lakhman, Yulia","roleDisplay":"VerfasserIn"},{"given":"Lora H.","family":"Ellenson","role":"aut","roleDisplay":"VerfasserIn","display":"Ellenson, Lora H."},{"role":"aut","display":"Tavaré, Simon","roleDisplay":"VerfasserIn","given":"Simon","family":"Tavaré"},{"family":"Aparicio","given":"Samuel","roleDisplay":"VerfasserIn","display":"Aparicio, Samuel","role":"aut"},{"given":"Dennis S.","family":"Chi","role":"aut","display":"Chi, Dennis S.","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Aghajanian, Carol","role":"aut","family":"Aghajanian","given":"Carol"},{"given":"Nadeem R.","family":"Abu-Rustum","role":"aut","roleDisplay":"VerfasserIn","display":"Abu-Rustum, Nadeem R."},{"family":"Friedman","given":"Claire F.","display":"Friedman, Claire F.","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Dmitriy","family":"Zamarin","role":"aut","display":"Zamarin, Dmitriy","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Weigelt, Britta","given":"Britta","family":"Weigelt"},{"family":"Bakhoum","given":"Samuel F.","roleDisplay":"VerfasserIn","display":"Bakhoum, Samuel F.","role":"aut"},{"family":"Shah","given":"Sohrab P.","roleDisplay":"VerfasserIn","display":"Shah, Sohrab P.","role":"aut"}],"relHost":[{"recId":"240151402","language":["eng"],"disp":"Ongoing genome doubling shapes evolvability and immunity in ovarian cancerNature","type":{"bibl":"newspaper","media":"Online-Ressource"},"note":["Gesehen am 19.02.2019"],"titleAlt":[{"title":"Nature <London>"},{"title":"Nature"}],"part":{"text":"644(2025), 8078, Seite 1078-1087, [1-29]","volume":"644","extent":"39","year":"2025","pages":"1078-1087, [1-29]","issue":"8078"},"pubHistory":["1.1869/70 - ; auch mit durchgehender Nr.-Zählung"],"title":[{"title":"Nature","subtitle":"international weekly journal of science","title_sort":"Nature"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["240151402"],"zdb":["1413423-8"],"issn":["1476-4687"]},"origin":[{"publisherPlace":"London [u.a.] ; London","publisher":"Nature Publ. Group ; Macmillan","dateIssuedKey":"1869","dateIssuedDisp":"1869-"}]}],"physDesc":[{"extent":"39 S.","noteIll":"Diagramme"}],"id":{"doi":["10.1038/s41586-025-09240-3"],"eki":["1942961596"]},"origin":[{"dateIssuedKey":"2025","dateIssuedDisp":"16 July 2025"}],"name":{"displayForm":["Andrew McPherson, Ignacio Vázquez-García, Matthew A. Myers, Duaa H. Al-Rawi, Matthew Zatzman, Adam C. Weiner, Samuel Freeman, Neeman Mohibullah, Gryte Satas, Marc J. Williams, Nicholas Ceglia, Danguolė Norkūnaitė, Allen W. Zhang, Jun Li, Jamie L.P. Lim, Michelle Wu, Seongmin Choi, Eliyahu Havasov, Diljot Grewal, Hongyu Shi, Minsoo Kim, Roland F. Schwarz, Tom Kaufmann, Khanh Ngoc Dinh, Florian Uhlitz, Julie Tran, Yushi Wu, Ruchi Patel, Satish Ramakrishnan, DooA Kim, Justin Clarke, Hunter Green, Emily Ali, Melody DiBona, Nancy Varice, Ritika Kundra, Vance Broach, Ginger J. Gardner, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Sarah H. Kim, Rachel N. Grisham, Ying L. Liu, Agnes Viale, Nicole Rusk, Yulia Lakhman, Lora H. Ellenson, Simon Tavaré, Samuel Aparicio, Dennis S. Chi, Carol Aghajanian, Nadeem R. Abu-Rustum, Claire F. Friedman, Dmitriy Zamarin, Britta Weigelt, Samuel F. Bakhoum & Sohrab P. Shah"]}} | ||
| SRT | |a MCPHERSONAONGOINGGEN1620 | ||