Projects we fund

Overview

In this project, Sarah Farndon (pictured above) is undertaking a whole genome study of two children with bilateral neuroblastoma, with the aim of reconstructing the life history of each tumour – that is, finding out how it started and how it developed. She will study each child’s DNA, as well as their parents’ DNA so that they can establish the precise order in which genetic mutations happened, and work out what caused each mutation – in order to work out what caused the neuroblastoma to form. We already know that there are different types of mutation. ‘Germline’ mutations are inherited from the parents and a present at conception. Somatic mutations are alterations that occur in the DNA after a child is conceived, and Sarah will look for somatic mutations which are shared by both tumours, as well as any that are unique to each tumour, in order to get a complete picture of the history of each neuroblastoma in the study. By studying pairs of bilateral tumours, we may be able to identify common sequences of events in each tumour – which could mean that our findings reveal early mutations which are common to both tumours and might be targets for treating these tumours in the future.

Potential impact

Sarah hopes that by gaining a complete picture of how these tumours developed, she might be able to identify mutations which happened at an early stage which give us clues to how to treat this cancer in the future. By defining the precise order of events in which the tumour develops, she may be able to help develop a ‘recipe’ for the genetic pathway which can cause neuroblastoma to develop. Once we understand this pathway better, we may be able to use it as a basis for future research using larger numbers of neuroblastoma samples in order to increase our understanding of these tumours. If successful, being able to predict how a tumour evolves would be of huge benefit to doctors treating children with neuroblastoma and other types of cancer, as it will enable them to know how it will develop, and its likely response to treatment. In the case of those tumours which are inherited by children from parents, it may also enable us to screen future generations and identify those at risk of developing the disease. This study will also explore what additional insights might be gained from defining mosaic mutations in childhood tumours, which would represent an important methodological shift for childhood cancer sequencing projects, including the UK’s 100,000 Genome project.