Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Impact of genomic heterogeneity and mutation patterns on the outcome of patients with epithelial ovarian cancer (EOC)

Date

08 Oct 2016

Session

Poster Display

Presenters

Vassiliki Kotoula

Citation

Annals of Oncology (2016) 27 (6): 296-312. 10.1093/annonc/mdw374

Authors

V. Kotoula1, S. Lakis1, E. Giannoulatou2, G. Kouvatseas3, G. Lazaridis1, I. Tikas1, I. Efstratiou1, S. Chrisafi1, E. Charalambous1, A. Papanikolaou1, F. Fostira1, B. Tarlatzis1, G. Fountzilas1

Author affiliations

  • 1 Data Office, Hellenic Cooperative Oncology Group (HeCOG), 11524 - Athens/GR
  • 2 Bioinformatics, Victor Chang Cardiac Research Institute, Darlinghurst/AU
  • 3 Biostatistics, Health Data Specialists Ltd, Athens/GR
More

Resources

Background

EOC often display genomic heterogeneity and mutations associated with homologous recombination repair deficiency (HRD), which may have prognostic/predictive relevance. In the present study, we examined the mutational evolution in EOC and its association with patient outcome.

Methods

We examined coding mutations in 306 paraffin tissue samples from 69 patients with stage III-IV EOC treated with standard chemotherapy. The samples (2-9 per patient) were derived from normal salpinx epithelium (N), primary tumors (P) and metastatic sites (M). Coding regions in 39 EOC-related genes were sequenced at high depth (mean 2739; median 2362) and a genomic heterogeneity index (HGi) was calculated. Progression-free survival (PFS) was the clinical endpoint.

Results

In 64/69 patients, at least 2 paired N, P and M samples shared 640 mutations (16% of all mutations) in 15 genes. Shared mutations (s-mut) exhibited higher allelic frequency as compared to private ones (all p 

Conclusions

A temporal mutation order in the evolution of EOC is suggested; HRD mutations seem important in the transition from normal to primary tumor and TP53 mutations in metastatic spread. Genomic heterogeneity seems to interact with tumor histology and shared normal/tumor HRD mutations for patient prognosis. Validation in larger patient series is needed.

Clinical trial identification

N/A

Legal entity responsible for the study

Hellenic Cooperative Oncology Group

Funding

Astra-Zeneca S.A.

Disclosure

All authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings