Digital Public Defence: Marta Brunetti
MSc Marta Brunetti at Institute of Clinical Medicine will be defending the thesis “High-grade serous carcinoma and related tumors: molecular analysis of potential targets” for the degree of PhD (Philosophiae Doctor).
Photo: Francesco Barbella
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital Trial Lecture – time and place
- First opponent: Professor Fernando Schmitt, IPATIMUP, Medical Faculty, University of Porto, Portugal
- Second opponent: Professor Camilla Krakstad, Department of Clinical Science, University of Bergen
- Third member and chair of the evaluation committee: Professor Therese Sørlie, Faculty of Medicine, University of Oslo
Chair of the Defence
Associate Professor June Helen Myklebust, Faculty of Medicine, University of Oslo
Professor II Ben Davidson, Faculty of Medicine, Faculty of Medicine, University of Oslo
High-grade serous carcinoma, the most common and aggressive type of ovarian cancer, and the related entity carcinosarcoma have a particular way of metastasizing within the serosal cavities with the accumulation of fluid, forming malignant ascites and pleural effusions. Despite improvements in therapy, the emergence of drug-resistant disease is a major problem in clinical management. There is little knowledge about the molecular profile of these metastatic cells, and a better understanding of disease progression in these cancers is necessary for improving the poor outcome of these patients.
The characterization of genes, mRNAs, miRNAs, and proteins is useful in generating diagnostic and prognostic markers and in better understanding their clinical utility and significance.
The aim of this thesis was to improve the molecular characterization of metastatic ovarian cancer and investigate tumor heterogeneity identifying case-specific profiles.
Different molecular methods were used to assess nucleic acid status (DNA at mutation status, mRNA, and miRNAs at expression level) and protein expression of various tumor-associated molecules.
Analysis of the somatic mutation profile of tumor cells in effusions identified TP53 as the most frequent mutated gene.
Expression of the dipeptidyl proteases DPP8 and DPP9, the chromatin remodeling genes and proteins HMGA1/2 and DAXX, and miRNAs targeting the chromatin remodeling genes showed correlation with clinical parameters.
Methylation of the MGMT gene promoter, a process that inhibits gene transcription and protein synthesis, was a rare epigenetic change in tumor cells in effusions.
Overall, there are still many unresolved questions regarding metastatic ovarian cancer, and tumor heterogeneity still represents a significant challenge.
These findings may close some of the gaps between molecular biology and clinical approaches.
Contact the research support staff.