A1 Refereed original research article in a scientific journal
Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer
Authors: Perez-Villatoro Fernando, Oikkonen Jaana, Casado Julia, Chernenko Anastasiya, Gulhan Doga C., Tumiati Manuela, Li Yilin, Lavikka Kari, Hietanen Sakari, Hynninen Johanna, Haltia Ulla-Maija, Tyrmi Jaakko S., Laivuori Hannele, Konstantinopoulos Panagiotis A., Hautaniemi Sampsa, Kauppi Liisa, Färkkilä Anniina
Publisher: Nature Portfolio
Publication year: 2022
Journal: npj Precision Oncology
Journal name in source: NPJ PRECISION ONCOLOGY
Journal acronym: NPJ PRECIS ONCOL
Article number: 96
Volume: 6
Number of pages: 13
eISSN: 2397-768X
DOI: https://doi.org/10.1038/s41698-022-00339-8(external)
Web address : https://doi.org/10.1038/s41698-022-00339-8(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/178371373(external)
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.
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