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Project

Translational genomics of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive cancer originating from the mesothelial cells of the pleura. A causal relationship between the development of MPM and exposure to asbestos has been demonstrated, with up to 80% of all patients being exposed in the past. Taking into account the long latency (± 40 years) between asbestos exposure and MPM-development, and considering the continued use of asbestos in some non-Western and developing countries, MPM will remain a global health issue for years to come. Despite improvements in outcome with the advent of -palliative- chemotherapy, MPM-patients still face a very poor prognosis. Hence, there is ample room for the development of novel treatment strategies. The presented project focuses on investigating the use of next-generation sequencing techniques for the detection of genetic changes in mesothelioma cells, gathered both by solid and liquid biopsy. These genetic alterations might then have the potential to be targeted by new and innovative medication types. To achieve this, mesothelioma tissue, collected during a solid biopsy, will be investigated for the presence of genetic alterations that are not present in matched normal material. In this respect, copy number changes will be studied using low-pass whole genome sequencing, whereas point mutations and small insertions and deletions will be detected by means of whole exome sequencing. Potentially actionable alterations that are traced in this way, will be validated in an external patient group. Hereafter, the possibility of detecting these actionable mutations in easily and repeatedly accessible liquid biopsies (i.e. in circulating tumor DNA) will be studied. We are convinced that the aims pursued in this project will contribute to the identification of differences between normal and transformed mesothelial cells, that will have the potential to be targeted by new medication.
Date:1 Oct 2015 →  30 Sep 2018
Keywords:GENOMICS, MESOTHELIOMA
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other clinical sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences