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

Fernando Perez-Villatoro, Jaana Oikkonen, Julia Casado, Anastasiya Chernenko, Doga C Gulhan, Manuela Tumiati, Yilin Li, Kari Lavikka, Sakari Hietanen, Johanna Hynninen, Ulla-Maija Haltia, Jaakko S Tyrmi, Hannele Laivuori, Panagiotis A Konstantinopoulos, Sampsa Hautaniemi, Liisa Kauppi, Anniina Färkkilä

Research output: Contribution to journalArticleScientificpeer-review


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.
Original languageEnglish
Article number96
Number of pages13
JournalNPJ precision oncology
Issue number1
Publication statusPublished - 29 Dec 2022
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 1


Dive into the research topics of 'Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer'. Together they form a unique fingerprint.

Cite this