Molecular tumour profiling by mass spectrometry (MS)

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The primary focus of this study will be investigation of molecular/mass spectral signatures associated with glioblastomas, a disease with a median survival rate of less than 15 months. The team will work with the clinical neuro-oncology team, accessing biopsy and resected tumour samples that have been imaged in vivo by PET and MR and ex vivo by immunohistochemistry and genetic profiling. Passages of these human-derived cell lines will be used to follow tumour evolution in preclinical xenograft models. The project therefore provides excellent multimodality data for comparison with the MS spectra and images.Collaborating with scientists at Waters (a University of Manchester strategic partner) will give access to both Desorption Electrospray Mass Spectrometry (DESI) and Rapid Evaporative Ionization Mass Spectrometry (REIMS) instrumentation. DESI and REIMS allow acquisition of mass spectra and MS images of tissues at ambient temperature, complementing other histopathological techniques. Our goal is to further develop tumour characterisation in terms of the heterogeneity of the tumour molecular/MS signature, through access to these new MS probe/imaging technologies, using multivariate statistical approaches to differentiate phenotypes within and between tumours, correlating the corresponding mass spectral signatures with data from the other imaging modalities and genetic profiles.We will test the hypothesis that MS interrogation of tumour samples can assist early diagnosis, surgical decision-making and the better understanding of mechanisms of disease progression. Outcomes will include a better understanding of tumour heterogeneity and evolution as well as the nature of the molecular signatures that characterise that heterogeneity or changes over time. We aim to better understand tissue spectra enhancing the capabilities of REIMS and DESI as tools for tumour staging, subtype identification and facilitate development of in situ probe technologies allowing tissue sampling in real-time during surgical procedures.Waters will also contribute in the form of a Case award.