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Evolutionary mode and timing of dissemination of high-grade serous carcinomas.
Sveen, Anita; Johannessen, Bjarne; Klokkerud, Solveig Mk; Kraggerud, Sigrid M; Meza-Zepeda, Leonardo A; Bjørnslett, Merete; Bischof, Katharina; Myklebost, Ola; Taskén, Kjetil; Skotheim, Rolf I; Dørum, Anne; Davidson, Ben; Lothe, Ragnhild A.
Afiliación
  • Sveen A; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Johannessen B; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Klokkerud SM; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Kraggerud SM; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Meza-Zepeda LA; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Bjørnslett M; Department of Tumor Biology, Institute for Cancer Research.
  • Bischof K; Genomics Core Facility, Department of Core Facilities, Institute for Cancer Research.
  • Myklebost O; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Taskén K; Department of Gynecological Oncology, The Norwegian Radium Hospital, and.
  • Skotheim RI; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Dørum A; Department of Tumor Biology, Institute for Cancer Research.
  • Davidson B; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Lothe RA; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
JCI Insight ; 9(3)2024 Jan 04.
Article en En | MEDLINE | ID: mdl-38175731
ABSTRACT
Dissemination within the peritoneal cavity is a main determinant of poor patient outcomes from high-grade serous carcinomas (HGSCs). The dissemination process is poorly understood from a cancer evolutionary perspective. We reconstructed the evolutionary trajectories across a median of 5 tumor sites and regions from each of 23 patients based on deep whole-exome sequencing. Polyclonal cancer origin was detected in 1 patient. Ovarian tumors had more complex subclonal architectures than other intraperitoneal tumors in each patient, which indicated that tumors developed earlier in the ovaries. Three common modes of dissemination were identified, including monoclonal or polyclonal dissemination of monophyletic (linear) or polyphyletic (branched) subclones. Mutation profiles of initial or disseminated clones varied greatly among cancers, but recurrent mutations were found in 7 cancer-critical genes, including TP53, BRCA1, BRCA2, and DNMT3A, and in the PI3K/AKT1 pathway. Disseminated clones developed late in the evolutionary trajectory models of most cancers, in particular in cancers with DNA damage repair deficiency. Polyclonal dissemination was predicted to occur predominantly as a single and rapid wave, but chemotherapy exposure was associated with higher genomic diversity of disseminated clones. In conclusion, we described three common evolutionary dissemination modes across HGSCs and proposed factors associated with dissemination diversity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Carcinoma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Carcinoma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: JCI Insight Año: 2024 Tipo del documento: Article País de afiliación: Noruega Pais de publicación: Estados Unidos