OI Ljubljana

Minimally invasive diagnostic approaches in brain tumours using circulating cell-free nucleic acids


Tumours of the central nervous system (CNS) are a group of tumours that develop in the brain and spinal cord, including the meninges, pituitary gland, pineal gland and nerves. The majority of primary CNS tumours are aggressive neoplasms, which despite radical treatment (usually a combination of surgery, radiotherapy and chemotherapy) recur frequently, often in a more malignant form. Progress in the molecular characterization of primary brain tumours has led to an extensive revision of the WHO classification of CNS tumours and to an update of the neuropathological assessment of brain tumours, which integrates histopathological features and molecular genetic tests for classification, prediction of biological behaviour and treatment decisions. The current main problem in the management of patients with primary brain tumours is the lack of effective strategies that could detect the disease at an early stage. In addition, these tumours are clinically and molecularly extremely heterogeneous neoplasms. Often several genes are altered, both at the genomic and transcriptomic level. The correct diagnosis and therapy selection due to the high tumour heterogeneity can therefore be difficult and inadequate, and lead to poor prognosis.

For the study, we will prospectively recruit 150-200 new patients with primary brain tumour and follow them from the initial diagnosis phase, through the treatment phase and during the monitoring phase. In each phase, we will collect plasma and cerebrospinal fluid (CSF, when available) samples together with detailed clinical-pathological information and develop new methods, such as digital droplet PCR-based custom assays for the ultrasensitive detection of cell-free tumour DNA and RNA in the blood and CSF of the patient. For broader biomarker detection in plasma and CSF, a method of next-generation sequencing pan-cancer panel will be used.

The main goal of the proposed research project is the implementation of minimally invasive diagnostics of patients with brain tumours. We will also compare detailed genetic data from patients' tissues and fluids to study the heterogeneity and evolution of tumours. By using next-generation sequencing panel, we will try to identify and monitor acquired drug resistance and the efficiency of treatment. Moreover, with the use of ultrasensitive digital droplet PCR, we will monitor minimal residual disease and recurrence. We aim that the final results will provide us with standardised tests and techniques needed for the early diagnosis of patients with brain tumours and for determining the response to treatment and follow-up.




© 2019 - Institute of Oncology Ljubljana
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