The dynamics of methylation in healthy ageing and premalignant disease

Summary

DNA methylation is emerging as a highly sensitive and specific marker of cancer initiation and progression. How these cancer-specific methylation changes are established in the decades before cancer and how these differ from methylation changes expected during healthy ageing, however, remains largely unknown.

Project aims

The aim of this project will be mine a unique methylation sequencing data set generated from longitudinal blood samples collected annually up to 15 years prior to a diagnosis of acute myeloid leukaemia where the dynamics of AML-specific methylation changes have been sensitively tracked with high temporal resolution.

By comparing these dynamics with data generated from people who never develop cancer we aim to develop a population genetic framework to describe the dynamics of methylation and use this framework to discover cancer-specific methylation changes.

By combining these data with longitudinal measurements of somatic genetic variants in the same samples the aim will be to distinguish between shared “driver” alterations that reflect early epigenetic re-programming associated with cancer development and large numbers of stochastic “passenger” events that reflect random epimutation.

Contact details

Dr Jamie Blundell - jrb75@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD