Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer.

Autor: Perez-Villatoro F; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.; iCAN digital precision cancer medicine flagship, Helsinki, Finland., Oikkonen J; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Casado J; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.; iCAN digital precision cancer medicine flagship, Helsinki, Finland., Chernenko A; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.; iCAN digital precision cancer medicine flagship, Helsinki, Finland., Gulhan DC; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Tumiati M; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Li Y; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Lavikka K; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Hietanen S; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland., Hynninen J; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland., Haltia UM; Department of Obstetrics and Gynecology, Helsinki University and Helsinki University Hospital, Helsinki, Finland., Tyrmi JS; Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland., Laivuori H; Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; Department of Obstetrics and Gynaecology, Tampere University Hospital, Tampere, Finland.; Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland., Konstantinopoulos PA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA., Hautaniemi S; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland., Kauppi L; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland.; Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland., Färkkilä A; Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland. anniina.farkkila@helsinki.fi.; iCAN digital precision cancer medicine flagship, Helsinki, Finland. anniina.farkkila@helsinki.fi.; Department of Obstetrics and Gynecology, Helsinki University and Helsinki University Hospital, Helsinki, Finland. anniina.farkkila@helsinki.fi.
Jazyk: angličtina
Zdroj: NPJ precision oncology [NPJ Precis Oncol] 2022 Dec 29; Vol. 6 (1), pp. 96. Date of Electronic Publication: 2022 Dec 29.
DOI: 10.1038/s41698-022-00339-8
Abstrakt: Homologous recombination DNA-repair deficiency (HRD) is a common driver of genomic instability and confers a therapeutic vulnerability in cancer. The accurate detection of somatic allelic imbalances (AIs) has been limited by methods focused on BRCA1/2 mutations and using mixtures of cancer types. Using pan-cancer data, we revealed distinct patterns of AIs in high-grade serous ovarian cancer (HGSC). We used machine learning and statistics to generate improved criteria to identify HRD in HGSC (ovaHRDscar). ovaHRDscar significantly predicted clinical outcomes in three independent patient cohorts with higher precision than previous methods. Characterization of 98 spatiotemporally distinct metastatic samples revealed low intra-patient variation and indicated the primary tumor as the preferred site for clinical sampling in HGSC. Further, our approach improved the prediction of clinical outcomes in triple-negative breast cancer (tnbcHRDscar), validated in two independent patient cohorts. In conclusion, our tumor-specific, systematic approach has the potential to improve patient selection for HR-targeted therapies.
(© 2022. The Author(s).)
Databáze: MEDLINE
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