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Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.
Rosendahl Huber, Axel; Pleguezuelos-Manzano, Cayetano; Puschhof, Jens; Ubels, Joske; Boot, Charelle; Saftien, Aurelia; Verheul, Mark; Trabut, Laurianne T; Groenen, Niels; van Roosmalen, Markus; Ouyang, Kyanna S; Wood, Henry; Quirke, Phil; Meijer, Gerrit; Cuppen, Edwin; Clevers, Hans; van Boxtel, Ruben.
Afiliación
  • Rosendahl Huber A; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Carrer de Baldiri Reixac, 10, 08028 Barcelona, Spa
  • Pleguezuelos-Manzano C; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Puschhof J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electroni
  • Ubels J; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Boot C; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Saftien A; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Verheul M; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Trabut LT; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Groenen N; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • van Roosmalen M; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Ouyang KS; Microbiome and Cancer Division, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Wood H; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
  • Quirke P; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
  • Meijer G; Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Cuppen E; University Medical Center Utrecht, Utrecht, the Netherlands; Hartwig Medical Foundation, Amsterdam, the Netherlands.
  • Clevers H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands; Roche Pharmaceutical Research and Early Development, 4058 Basel, Switzerland. Electronic address: h.clevers@hubrecht.eu.
  • van Boxtel R; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands. Electronic address: r.vanboxtel@prinsesmaximacentrum.nl.
Cancer Cell ; 42(3): 487-496.e6, 2024 Mar 11.
Article en En | MEDLINE | ID: mdl-38471458
ABSTRACT
Co-culture of intestinal organoids with a colibactin-producing pks+E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+E. coli strains.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neoplasias Colorrectales / Escherichia coli / Policétidos Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Neoplasias Colorrectales / Escherichia coli / Policétidos Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos