Optimized detection of homologous recombination deficiency improves the prediction of clinical outcomes in cancer
Year: 2022
Type: article
Study design: Observational Study
Abstract: 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.
Source: npj Precision Oncology
Authors: 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
Institutions: University of Helsinki, Harvard University, University of Turku, Turku University Hospital, Helsinki University Hospital, Tampere University, University of Tampere, University of Oulu, Tampere University Hospital, Institute for Molecular Medicine Finland, HiLIFE – Elämäntieteiden Instituutti, Dana-Farber Cancer Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,390
Awards: G1511762080, Suppression Of underwater Noise Induced by Cavitation, G434337789, G6373015536, Comprehensive characterization and effective combinatorial targeting of high-grade serous ovarian cancer via single-cell analysis, Improved clinical decisions via integrating multiple data levels to overcome chemotherapy resistance in high-grade serous ovarian cancer
OpenAlex ID: W4313332611