Academic research community (GECIP)

DNA and RNA are the genetic material carrying the instructions used in human development, normal functioning and reproduction. RNA plays a vital role in controlling when and where particular genes are expressed. Our research laboratory discovers and characterises new RNA molecules in cancer and how clinical intervention of these RNAs may represent new therapeutic strategies.

Cancers result from an evolutionary process, akin to the Darwinian process driving the evolution of species. In this project we aim to leverage on mathematical techniques we have recently developed to measure this process in human cancers. This will allow to make sense to the data in light of tumour evolution, but also to potentially identify new prognostic biomarkers that will be useful for patient stratification.

Congenital melanocytic naevi (CMN) is a rare disease in which moles are present at birth on the skin and sometimes in the brain. It predisposes affected children to melanoma. We are investigating the genetics of CMN to try to improve our understanding of the condition and to help direct our search for treatments.

We will look for genetic changes in children’s high-grade tumours, which may explain how and why these tumours develop.

Next generation sequencing technologies have had a significant impact on our understanding of the driving events underlying paediatric tumours. However, for low-grade paediatric tumours there is a relative paucity of understanding in this regard when compared to their high-grade counterparts. In particular, the identification of key genetic events in low-grade tumours has the potential to identify novel entities and improve treatments through a better understanding of their underlying biology. To that end, in this project we will interrogate whole genome sequencing data from patients with paediatric low-grade tumours, with a particular focus on rare diagnoses, to identify recurrent genetic abnormalities associated with these tumours.

Childhood cancers are believed to be more strongly linked to inherited gene alterations compared to adult cancers, where family background explains only a small proportion of patient cases. We will use genomic data available from Genomics England to examine the genetic variations that predispose these children to cancer. This work will help to better understand the causes of cancer in childhood, aid the earlier diagnosis, therapy and possibly even pave the way to a cure for children at the initial stages of developing these cancers.

The team submitting this application is the Data Sciences group within the Oncology therapeutic area (study and treatment of tumours) of Servier Pharmaceuticals (Boston, MA, US), headed by Stefan Kirov (see mini-CV). Our team is comprised of 5 bioinformatics analysts, and we transitioned to Servier during the Agios Pharmaceuticals oncology acquisition in April 2021. As part of Agios, our group used diverse in-house and public genomic datasets to deliver multiple hypotheses for new protein targets in defined subsets of cancers.