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Senior Bioinformatic Analyst/Bioinformatic Analyst Circulating tumour DNA analysis

Recent papers and comments
Annals of Oncology (1st May 2022) - Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer

Scientific Reports (4th February 2022) - Refined characterization of circulating tumor DNA through biological feature integration

Genome Research (February 2022) - Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA

EMBO Molecular Medicine (22nd July 2021) - Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients

Science Translational Medicine (17th June 2020) - ctDNA monitoring using patient-specific sequencing and integration of variant reads
With a lay summary in The Conversation

Clinical Chemistry (8th April 2020) - Detection of ctDNA from Dried Blood Spots after DNA Size Selection

Genome Medicine (27th Feb 2020) - Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

Science Translational Medicine (7th Nov 2018) - Enhanced detection of circulating tumor DNA by fragment size analysis
With a commentry by Heitzer and Speicher and cover art
*** Highlighted in the The American Association for the Advancement of Science SPECIAL EDITION: Cancer ***
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

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

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
Gale D, Heider K, Ruiz-Valdepenas A, Hackinger S, Perry M, Marsico G, Rundell V, Wulff J, Sharma G, Knock H, Castedo J, Cooper W, Zhao H, Smith CG, Garg S, Anand S, Howarth K, Gilligan D, Harden SV, Rassl DM, Rintoul RC, Rosenfeld N. Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer. Ann Oncol. 2022 May;33(5):500-510. DOI: 10.1016/j.annonc.2022.02.007

Markus H, Chandrananda D, Moore E, Mouliere F, Morris J, Brenton JD, Smith CG, Rosenfeld N. Refined characterization of circulating tumor DNA through biological feature integration. Sci Rep. 2022 Feb 4;12(1):1928. DOI: 10.1038/s41598-022-05606-z

Hudecova I, Smith CG, Hänsel-Hertsch R, Chilamakuri CS, Morris JA, Vijayaraghavan A, Heider K, Chandrananda D, Cooper WN, Gale D, Garcia-Corbacho J, Pacey S, Baird RD, Rosenfeld N, Mouliere F. Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA. Genome Res. 2022 Feb;32(2):215-227. DOI: 10.1101/gr.275691.121

See all publications

Cancer Research UK Cambridge Institute website