High resolution clonal architecture of hypomutated Wilms tumours
Abstract A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resoluti...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59854-4 |
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| author | Henry Lee-Six Taryn D. Treger Manas Dave Tim HH Coorens Nathaniel D. Anderson Yvonne Tiersma Sepide Derakhshan Sanne de Haan Marry M. van den Heuvel-Eibrink Yichen Wang Anna Wenger Reem Al-Saadi Alice Lawford Aleksandra Letunovska Jenny Wegert Conor Parks Guillaume Morcrette Manfred Gessler Gordan Vujanic Tanzina Chowdhury Maureen J O’Sullivan Ronald R. de Krijger Michael R. Stratton Kathy Pritchard-Jones J. Ciaran Hutchinson Jarno Drost Sam Behjati |
| author_facet | Henry Lee-Six Taryn D. Treger Manas Dave Tim HH Coorens Nathaniel D. Anderson Yvonne Tiersma Sepide Derakhshan Sanne de Haan Marry M. van den Heuvel-Eibrink Yichen Wang Anna Wenger Reem Al-Saadi Alice Lawford Aleksandra Letunovska Jenny Wegert Conor Parks Guillaume Morcrette Manfred Gessler Gordan Vujanic Tanzina Chowdhury Maureen J O’Sullivan Ronald R. de Krijger Michael R. Stratton Kathy Pritchard-Jones J. Ciaran Hutchinson Jarno Drost Sam Behjati |
| author_sort | Henry Lee-Six |
| collection | DOAJ |
| description | Abstract A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We find that apparent hypomutation is the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged. |
| format | Article |
| id | doaj-art-2e7335bbea9e4e88b916f29ff8c27ae1 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2e7335bbea9e4e88b916f29ff8c27ae12025-08-20T02:00:07ZengNature PortfolioNature Communications2041-17232025-05-0116111010.1038/s41467-025-59854-4High resolution clonal architecture of hypomutated Wilms tumoursHenry Lee-Six0Taryn D. Treger1Manas Dave2Tim HH Coorens3Nathaniel D. Anderson4Yvonne Tiersma5Sepide Derakhshan6Sanne de Haan7Marry M. van den Heuvel-Eibrink8Yichen Wang9Anna Wenger10Reem Al-Saadi11Alice Lawford12Aleksandra Letunovska13Jenny Wegert14Conor Parks15Guillaume Morcrette16Manfred Gessler17Gordan Vujanic18Tanzina Chowdhury19Maureen J O’Sullivan20Ronald R. de Krijger21Michael R. Stratton22Kathy Pritchard-Jones23J. Ciaran Hutchinson24Jarno Drost25Sam Behjati26Wellcome Sanger InstituteWellcome Sanger InstituteWellcome Sanger InstituteBroad Institute of MIT and HarvardWellcome Sanger InstitutePrincess Máxima Center for Pediatric OncologyPrincess Máxima Center for Pediatric OncologyPrincess Máxima Center for Pediatric OncologyPrincess Máxima Center for Pediatric OncologyWellcome Sanger InstituteWellcome Sanger InstituteUCL Great Ormond Street Institute of Child HealthGreat Ormond Street Hospital for ChildrenUCL Great Ormond Street Institute of Child HealthTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center MainfrankenWellcome Sanger InstituteUCL Great Ormond Street Institute of Child HealthTheodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center MainfrankenDepartment of Pathology, Sidra MedicineUCL Great Ormond Street Institute of Child HealthDepartment of Pathology, Children’s Health Ireland at CrumlinPrincess Máxima Center for Pediatric OncologyWellcome Sanger InstituteUCL Great Ormond Street Institute of Child HealthGreat Ormond Street Hospital for ChildrenPrincess Máxima Center for Pediatric OncologyWellcome Sanger InstituteAbstract A paradigm of childhood cancers is that they have a low mutation burden, with some ostensibly bearing fewer mutations than the normal tissues from which they derive. We set out to resolve this paradox by examining paediatric renal cancers with exceptionally few mutations using high resolution, high depth sequencing approaches. We find that apparent hypomutation is the result of unusual clonal architecture due to a normal tissue-like mode of tumour evolution, raising the possibility that the mutation burden of some cancers has been systematically misjudged.https://doi.org/10.1038/s41467-025-59854-4 |
| spellingShingle | Henry Lee-Six Taryn D. Treger Manas Dave Tim HH Coorens Nathaniel D. Anderson Yvonne Tiersma Sepide Derakhshan Sanne de Haan Marry M. van den Heuvel-Eibrink Yichen Wang Anna Wenger Reem Al-Saadi Alice Lawford Aleksandra Letunovska Jenny Wegert Conor Parks Guillaume Morcrette Manfred Gessler Gordan Vujanic Tanzina Chowdhury Maureen J O’Sullivan Ronald R. de Krijger Michael R. Stratton Kathy Pritchard-Jones J. Ciaran Hutchinson Jarno Drost Sam Behjati High resolution clonal architecture of hypomutated Wilms tumours Nature Communications |
| title | High resolution clonal architecture of hypomutated Wilms tumours |
| title_full | High resolution clonal architecture of hypomutated Wilms tumours |
| title_fullStr | High resolution clonal architecture of hypomutated Wilms tumours |
| title_full_unstemmed | High resolution clonal architecture of hypomutated Wilms tumours |
| title_short | High resolution clonal architecture of hypomutated Wilms tumours |
| title_sort | high resolution clonal architecture of hypomutated wilms tumours |
| url | https://doi.org/10.1038/s41467-025-59854-4 |
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