909P - The frequencies and clinical implications of mutations in kinase-related genes in ovarian cancer

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Ovarian Cancer
Translational Research
Presenter Aine O'Reilly
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors A. O'Reilly1, A. Mahmoud2, L. Grogan3, O.S. Breathnach4, P. Byrne5, B. Gaughan5, A. Carr2, E. Kay6, J.P. Crown7, S. Twomey8, B. Hennessy4
  • 1Dept Of Medical Oncology, Beaumont Hospital, 9 - Dublin/IE
  • 2-, Royal College of Surgeons Ireland, 2 - Dublin/IE
  • 3Department Of Medical Oncology, Beaumont Hospital, 9 - Dublin/IE
  • 4Medical Oncology, Beaumont Hospital, 9 - Dublin/IE
  • 5Gynaecology, Beaumont Hospital, 9 - Dublin/IE
  • 6Pathology, Beaumont Hospital, 9 - Dublin/IE
  • 7-, St Vincents University Hospital, IE-4 - Dublin/IE
  • 8-, Royal College of Surgeons, Dublin/IE

Abstract

Aim

Background: Ovarian cancer is the commonest cause of gynecological associated cancer death. The majority of patients present with advanced disease. Over 80% of patients will respond to first-line optimal cytoreductive surgery and platinum based chemotherapy, however the majority reoccur. Here we investigated the association between genetic mutations in known cancer related signaling pathways with clinical and pathological variables in patients with ovarian cancer.

Methods

DNA samples of patients with ovarian cancer were genotyped for Single Nucleotide Polymorphisms (SNPs) including potentially clinically relevant mutations such as PIK3CA, PIK3R1, PHLPP2, KRAS, PTPN11, CTNNB1, TP53 and NRAS using the Sequenom platform.

Results

15 patients with ovarian cancer were included in the study. Fourteen patients (93%) had at least one mutation identified. 5 patients (33%) had 2 or more mutations identified.Nine patients had serous histology (60%). SNPs identified in patients with serous histology were commonly associated with genes involved in the activation and regulation of the PIK3 pathway including PIK3CA (11%), PIK3R1 (22%) and PTPN11 (11%). SNPs in PHLPP2 a regulator of Akt kinases was common in patients with serous ovarian cancer (33%). The presence of mutations in TP53 was associated with non-serous histology (p = 0.01). Serous histology was associated with stage 3 or stage 4 disease at presentation (p < 0.01).Eight patients with serous histology were treated with platinum based chemotherapy, seven of these patients had optimal cytoreductive surgery. All patients subsequently recurred, with a median time PFS of 13.1 months and a median OS of 22.9 months. There was no statistically significant association identified between platinum free interval and mutations occurring in patients with serous histology. Similarly there was no statistically significant association identified between overall survival and gene mutations occurring in patients with serous ovarian cancer.

Conclusions

These results suggest that mutations in known cancer related signaling pathways occur frequently in patients with ovarian cancer but in our cohort failed to impact response to chemotherapy, platinum free interval or overall survival.

Disclosure

All authors have declared no conflicts of interest.