Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Comparative Assessment of Diagnostic Homologous Recombination Deficiency-Associated Mutational Signatures in Ovarian Cancer

Research output: Contribution to journalJournal articleResearchpeer-review

  1. B Cells and Tertiary Lymphoid Structures: Friends or Foes in Cancer Immunotherapy?

    Research output: Contribution to journalReviewResearchpeer-review

  2. A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Clinical Outcomes in Patients with Multi-Hit TP53 Chronic Lymphocytic Leukemia Treated with Ibrutinib

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Detection of Molecular Signatures of Homologous Recombination Deficiency in Bladder Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up†

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup

    Research output: Contribution to journalReviewResearchpeer-review

  3. Niraparib treatment for patients with BRCA-mutated ovarian cancer: review of clinical data and therapeutic context

    Research output: Contribution to journalReviewResearchpeer-review

View graph of relations

PURPOSE: Homologous recombination (HR) deficiency (HRD) is one of the key determinants of PARP inhibitor response in ovarian cancer, and its accurate detection in tumor biopsies is expected to improve the efficacy of this therapy. Because HRD induces a wide array of genomic aberrations, mutational signatures may serve as a companion diagnostic to identify PARP inhibitor-responsive cases.

EXPERIMENTAL DESIGN: From the The Cancer Genome Atlas (TCGA) whole-exome sequencing (WES) data, we extracted different types of mutational signature-based HRD measures, such as the HRD score, genome-wide LOH, and HRDetect trained on ovarian and breast cancer-specific sequencing data. We compared their performance to identify BRCA1/2-deficient cases in the TCGA ovarian cancer cohort and predict survival benefit in platinum-treated, BRCA1/2 wild-type ovarian cancer.

RESULTS: We found that the HRD score, which is based on large chromosomal alterations alone, performed similarly well to an ovarian cancer-specific HRDetect, which incorporates mutations on a finer scale as well (AUC = 0.823 vs. AUC = 0.837). In an independent cohort these two methods were equally accurate predicting long-term survival after platinum treatment (AUC = 0.787 vs. AUC = 0.823). We also found that HRDetect trained on ovarian cancer was more accurate than HRDetect trained on breast cancer data (AUC = 0.837 vs. AUC = 0.795; P = 0.0072).

CONCLUSIONS: When WES data are available, methods that quantify only large chromosomal alterations such as the HRD score and HRDetect that captures a wider array of HRD-induced genomic aberrations are equally efficient identifying HRD ovarian cancer cases.

Original languageEnglish
JournalClinical Cancer Research
Volume27
Issue number20
Pages (from-to)5681-5687
Number of pages7
ISSN1078-0432
DOIs
Publication statusPublished - 15 Oct 2021

Bibliographical note

©2021 American Association for Cancer Research.

ID: 70126254