Identifying biomarkers of transformation of low-grade astrocytoma using whole genome sequencing

Identifying biomarkers of transformation of low-grade astrocytoma by within-patient paired-sample whole-genome sequencing: integrating theranostics into specialist glioma healthcare

£74,834 (matched funding with NIHR Imperial BRC) Co-funded by the Alexander Jones Foundation in memory of Alexander Jones

Duration 9 months July 2013-March 2014, subsequently extended until August 2014 at no cost (completed)

Additional 6-month extension Sepember 2015-March 2016 (ongoing)

Investigators: Michael Johnson, Kevin O’Neill, Federico Roncaroli, Adam Waldman

Lay summary: Identifying and understanding the genetic events that drive brain tumors is critical for the development of effective diagnostic, prognostic and therapeutic strategies. For the vast majority of human malignancies, biopsy material is only available at a single stage of tumour development (e.g., once the tumour presents as a malignancy). In such cases, the identification of causal somatic mutations therefore requires sequencing in large sample sizes to identify genes mutated at statistically significant frequencies, as well as statistical inferences based on conservation across species, non-silent to silent mutation ratios, gene specific mutation rates, etc. However, almost uniquely uniquely in cancer research, the naturally occurring transformation of low-grade gliomas to high-grade tumors offers the potential to identify somatic mutation events driving transformation by sequencing the same tumor at its two critical stages (benign and malignant) of development.