Background

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Biology

Biology

Cell-free DNA (cfDNA) is released into the bloodstream by a combination of apoptosis, necrosis, and secretion within membrane-bound vesicles.

In healthy individuals, the majority of cfDNA is released from haematopoietic cells, though pathological tissues have been observed to increase their relative cfDNA release.

The half-life of circulating DNA in plasma has been measured as between 16 minutes and 2 hours, due to degradation and renal excretion.

Clinical utility of liquid biopsies

The concept of a “liquid biopsy” is that one could use blood (or other body fluids) to monitor any tumour material present in the systemic circulation. This has several potential uses, such as:

· Analysis to look for a specific mutation to allow use of a therapy targeted against that mutation, especially where it is not possible to obtain a tissue sample
· Monitoring of tumour burden or response to treatment
· Confirmation of the presence or absence of small amounts of residual cancer in patients being considered for adjuvant systemic therapies

Technologies

Approaches for ctDNA analysis range from hotspot mutation assays to whole-genome sequencing methods.

Droplet digital PCR-based methods achieve the highest per-locus sensitivity, though may target only a small number of loci. We aim to develop assays that achieve high sensitivity across a large number of mutations.

Previously, we developed Tagged amplicon-Sequencing, a targeted sequencing method for plasma DNA. We also showed that exome sequencing can be carried out in plasma.

 About

About

Aims
The Rosenfeld Lab employs emerging molecular technologies to develop new diagnostic approaches. Our focus is on circulating tumour DNA (ctDNA) as a noninvasive modality to assess evolution of solid malignancies. This is DNA originating from cancer cells, carrying tumour-specific genomic alterations, that is present as short cell-free fragments in body fluids such as blood plasma. ctDNA can be collected noninvasively via blood samples and has the potential to be immensely informative.

Recent Publications
Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, Pacey S, Baird S, Rosenfeld N. Liquid biopsies come of age: towards implementation of circulating tumour DNA Nat Rev Cancer. 2017 Apr;17(4):223-238. doi: 10.1038/nrc.2017.7. Epub 2017 Feb 24. Review.
Link to PDF

K. M. Patel, K. E. van der Vos, C. G. Smith, F. Mouliere, D. Tsui, J. Morris, D. Chandrananda, F. Marass, D. van den Broek, D. E. Neal, V. J. Gnanapragasam, T. Forshew, B. W. van Rhijn, C. E. Massie, N. Rosenfeld & M. S. van der Heijden Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer Scientific Reports 7, Article number: 5554 (2017) doi:10.1038/s41598-017-05623-3.

See all publications

Cancer Research UK Cambridge Institute website