Novel Adverse Genomic Rearrangement Signature in High-Grade Serous Ovarian Cancer

Key Points

  • A genomic rearrangement signature (Ov.RS3) was significantly associated with overall survival in high-grade serous ovarian cancer.
  • The signature did not have a high similarity with breast cancer signatures.

As reported by Hillman et al in the Journal of the National Cancer Institute, a novel genomic rearrangement signature associated with poorer overall survival has been identified in high-grade serous ovarian cancer.

Study Details

In the study, clinical data and whole-genome sequencing results were obtained for primary high-grade serous ovarian cancer tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). The cohort was dichotomized around median signature contribution to tumors, with overall survival being analyzed according to high vs low contribution. In an independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490), dichotomization was performed around median similarity between tumor copy number profile and prognostic rearrangement signatures.

Genomic Rearrangement Signatures

Overall, five genomic rearrangement signatures (Ov.RS1–5) were identified in the AOCS cohort. Ov.RS1, Ov.RS2, Ov.RS4, and Ov.RS5 were highly similar to signatures previously identified in breast cancer. No significant association with overall survival was observed for Ov.RS1 (hazard ratio [HR] = 1.08, P = .76), Ov.RS2 (HR = 0.75, P = .25), Ov.RS4 (HR = 1.05, P = .86), or Ov.RS5 (HR = 1.16, P = .55).

The remaining signature, Ov.RS3, did not have high similarity with breast cancer rearrangement signatures and was characterized by 10 kilobase to 10 megabase deletions and tandem duplications. Patients with tumors exhibiting high contribution from Ov.RS3 had a median overall survival of 22.7 months, compared with 38.0 months in patients with a low contribution from the signature (hazard ratio [HR] = 1.86, P = .02). In the TCGA cohort, median overall survival was 38.0 months in the Ov.RS3 high–similarity group vs 48.9 months in the Ov.RS3 low–similarity group (HR = 1.54, P < .001).

The investigators concluded: “A novel genomic rearrangement signature is associated with poor prognosis in [high-grade serous ovarian cancer]…. Prospective validation of the prognostic value of Ov.RS3 would result in a clinically applicable biomarker of [high-grade serous ovarian cancer] behavior. Such a biomarker could be used to identify patients with a poor prognosis who may be candidates for clinical trials in the adjuvant setting.”

The study was supported by the National Institutes of Health.

P. Andrew Futreal, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of the National Cancer Institute article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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