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13 Mucinous ovarian carcinoma: therapeutic options old and new
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  1. K Gorringe1,
  2. D Cheasley1,
  3. M Wakefield2,
  4. I Campbell1,
  5. Y Antill3,
  6. C Scott4,
  7. G GAMuT Collaborators1
  1. 1Peter MacCallum Cancer Centre, Research Division, Melbourne, Australia
  2. 2Walter and Eliza Hall Institute, Bioinformatics, Melbourne, Australia
  3. 3Cabrini Health, Oncology, Melbourne, Australia
  4. 4Walter and Eliza Hall Institute, Stem Cells and Cancer Division, Melbourne, Australia

Abstract

Objectives Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer subtype that responds poorly to conventional chemotherapy. Recurrent and advanced disease have poor survival and there are no specific guidelines for their treatment. We used a large cohort of genomic and immunohistochemical data to evaluate the likelihood of success of possible therapeutic interventions.

Methods We used DNA sequencing data (n=185) and genome-wide copy number (n=199) from primary MOC to identify key genetic events, homologous recombination deficiency scores and mismatch repair deficiency. Immunohistochemistry data was obtained for CK7, CK20, PAX8, p16, CDX2, HER2 and ER (n=162–256) and tumour infiltrating lymphocytes were counted on H&E stained slides (n=40).

Results Therapies exploiting homologous recombination deficiency are unlikely to be effective in MOC, as only 1.5% had a homologous recombination deficiency score of more than 50. Mismatch repair deficiency was very rare (<1%). Most cases had low lymphocytes counts, corresponding to a moderate mutation load. Events that suggest an existing targeted therapy include: ERBB2 amplification(26%), ERBB3 mutation(4%) and BRAF mutation(9%). Novel agents currently in clinical trials targeting genetic events such as TP53 missense mutation(46%), RNF43 mutation(11%), PIK3CA mutation(8%) and KRAS/NRAS mutations(66%).

Conclusions MOC is genetically diverse but with a number of potential targets. Importantly, the clinically observed lack of response to cisplatin is supported by a corresponding lack of a genomic signature, and MOC are unlikely to respond to PARP inhibitors. The role of immunotherapy is unclear. Testing novel therapeutic options in appropriate patient-derived models will be crucial and we are currently developing organoid cultures from this disease.

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