Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A feasibility study by Professor James McCullagh shows promise for biomarker discovery using a combination of circulating tumour DNA sequencing and metabolomic analysis.

In this paper published in the journal Cancers, Professor James McCullagh (Department of Chemistry) and colleagues investigate combining genetic and metabolic analysis to identify novel markers in blood plasma in the context of intrahepatic cholangiocarcinoma (ICC; bile duct cancer).

ICC is a rare but deadly cancer and most patients are diagnosed when the disease is at a late-stage, when the median survival is less than a year. Previous analysis has identified several DNA mutations, rearrangements and copy number variations in ICC. Of particular interest is a mutation of the enzyme isocitrate dehydrogenase (IDH) in 5-25% ICC cases, which leads to the production of the metabolite 2-hydroxyglutarate (2-HG). This increase in 2-HG affects a number of cellular processes involved in cancer initiation, which has led to 2-HG being labelled as an ‘oncometabolite’. Since IDH is a potential target for treatment in ICC and a number of other cancers, identification of IDH mutations and 2-HG can not only help to detect the presence of cancer but may also be able to direct treatment selection.

This proof-of-principle study used genomic and untargeted metabolomic analysis of plasma samples from ICC and healthy patients. ICC patients had altered metabolic profiles and the researchers were able to detect an IDH mutation in one of the four patients with ICC, in accordance with the known mutation incidence rate. Importantly, this patient also had a corresponding increase in 2-HG. These promising observations now need to be validated using a larger cohort study.


Similar stories

Funded DPhil studentships in early detection available - apply now for October 2023 entry

Oxford research groups are recruiting DPhil candidates for the funded DPhil in Cancer Science commencing in October 2023.

First DeLIVER study day

On Wednesday 8th June 2022, the DeLIVER consortium gathered for the first time to hear about the team’s progress towards the aim of detecting liver cancer earlier.