Allele-specific transcription of tumorigenic mutations in paediatric cancers

The Next Generation Precision Medicine Program focuses on utilising genetic profiles of patients’ tumour models to identify new therapeutic targets and repurpose existing ones using high-throughput functional CRISPR screens. Advancements in next-generation sequencing and computational biology techniques have facilitated a deeper understanding of the genetic underpinnings of cancers, paving the way for the advent of the next generation of targeted therapy for paediatric tumours. However, less than 15% of paediatric cancer patients harbour actionable mutations, of which fewer respond to targeted therapies. This underscores an urgent need to delve beyond driver mutations to identify biomarker coupled therapies. Transcriptomics not only enable characterisation of genetic alterations at the RNA level but also quantitatively capture how tumorigenic genotypes are transcribed into the malignant phenotype. It has been shown that allele-specific expression result in preferential expression of mutant or wild-type products. Using best-practice computational pipelines running on high-performance computers, the successful candidate will firstly identify the genetic alterations in a large compendium of patient derived tumour models. Secondly, they will then identify allele-specific expression of these key driver mutations. This project aims to describe whether allele specific expression contributes to tumorigenesis and identify the underlying mechanisms that unbalance transcription between alleles.