Projects & Publications

The Oxford Molecular Diagnostics Centre runs and supports a wide range of projects from clinical trials to global health programmes. Find out more about the work that we do below.

Global Health

AI-REAL (Aggressive Infection-Related East Africa Lymphoma)

At present, 95% of global child lymphoma blood cancers cases are found in sub-Saharan Africa. A subsection of blood cancers known as Epstein-Barr Virus-related lymphomas (or EBV lymphomas) are particularly aggressive, and have become the focus of AI-REAL; a new international global health collaboration which hopes to improve EBV lymphoma treatment and diagnosis.

Prof. Anna Schuh leads this UK-Africa project, which aims to bring the next generation of diagnosis technology to Tanzania and Uganda. Prof. Schuh hopes the in-country testing process for EBV lymphomas can be improved in order to improve early diagnosis and chances of survival.

Training in liquid biopsies is provided, to detect circulating tumour DNA in patients’ bloodstreams to determine the presence of virus-associated cancers such as EBV-driven lymphomas. Liquid biopsies are a new diagnostic technique which are significantly less invasive and are a recent result of new research from Schuh’s team.

New equipment and training programs have already been established in the four project sites, whilst live-streaming technology will be employed to share the knowledge of diagnostic clinicians in the UK with those in Uganda and Tanzania.

EBV driven lymphomas are treatable if caught early. It is the hope of this project that, through earlier detection and advanced technology training, the current 90% death rate seen in children with this kind of blood cancer can become a 90% cure rate.

This project was launched in February 2020, and is a partnership between the University of Oxford and medical teams in the Muhimbili National Hospital, Kilimanjaro Christian Medical Centre, St Mary’s Hospital (Lacor) and Muhimbili University of Health and Allied Sciences, with funding from the NIHR RIGHT Programme.

Clinical Trials

OxPLoreD

The purpose of the Oxford Pre-Cancerous Lymphoproliferative Disorders: Analysis and Interception study (OxPLoreD) is to learn more about people with early stage lymphoproliferative disorders. These are conditions where the immune system is not entirely normal and may produce abnormal lymphocytes (a type of white blood cell) or proteins in the blood. The majority of individuals with lymphoproliferative abnormalities do not experience any serious effect on their health, however a small number do go on to develop more serious conditions, such as blood or bone marrow cancers. Out of a hundred people with the pre-cancerous lymphoproliferative disorders, only one or two per year will go on to develop blood or bone marrow cancer. Currently, we do not have a reliable way to predict which individuals with these disorders are more likely to develop a blood or bone marrow cancer. The OMDC is leading this study into the identification of novel biomarkers in liquid biopsies to predict disease progression.

SCAN

The Oxford Suspected Cancer (SCAN) Pathway aims to reduce the time that patients who have vague symptoms that could be cancer wait to be diagnosed. The aim is to increase the number of patients that are diagnosed at an early stage in their illness. With faster and earlier diagnosis improving the patients experience of being diagnosed. The pathway involves GPs in Oxfordshire referring all patients aged 40 and over with vague symptoms to the SCAN Pathway if the GP thinks there is a chance they have cancer. These patients will quickly be given blood tests, a stool test, and a CT scan. The OMDC is supporting this study by co-ordinating the bio-banking and analysis of liquid biopsies from these patients.

STELLAR

The OMDC are the lead academic and sample processing laboratory for STELLAR, a phase II trial of patients with newly diagnosed or relapsed Richter’s syndrome. Transformation of chronic lymphocytic leukaemia (CLL) to diffuse large B-cell lymphoma (DLCBL) type Richter’s syndrome (RS) carries a dismal prognosis. Standard-of-care chemoimmunotherapy for de novo RS is inadequate with median survival of less than one year. Patients are frequently elderly or have co-morbidities limiting dose-intense chemotherapy. Treatment of relapsed/refractory (R/R) RS and RS emerging after CLL-directed therapy represent urgent unmet clinical needs. Agents targeting Bruton’s tyrosine kinase (BTK) deliver improved outcomes for patients with high-risk CLL and expand effective treatments to frailer patients. Acalabrutinib is an oral, second-generation BTK inhibitor with a favourable toxicity profile and demonstrated activity in CLL and B-cell lymphomas. Combination of acalabrutinib with standard-of-care CHOP-R chemoimmunotherapy offers a sound rationale to test in a prospective trial for de novo RS.

Research Projects

In the project below, custom made sequencing panels are being used to profile ctDNA.

These panels have been designed by the OMDC and tailored in strong partnership with specialists and suppliers of molecular detection products:

Dr. Jenny Taylor, Wellcome Centre for Human Genetics

Mutation profiling of circulating tumour DNA to inform prognosis and treatment selection for head and neck cancers

Dr Beth Psaila, NDCLS, Prof. Tim Maughan, Dept. of Oncology

Development of a novel targeted panel for the sequencing of ctDNA in solid tumour cancer patients. (ArcherDx)

Dr. Graham Collins, Dept. of Oncology

Detection of circulating DNA tumour in newly diagnosed Hodgkin lymphoma patients

Constoria

Precision Medicine for Aggressive Lymphomas (PMAL)

The Precision Medicine for Aggressive Lymphomas (PMAL) consortium is a national multi-partner network, established to develop robust predictive molecular assays for patients with high grade lymphomas and to optimise their treatment through trials of novel targeted therapy based on the results.

Biopsy samples from patients with lymphoma are studied by genomic, transcriptomic, molecular and immunophenotypic analysis, to establish their precise sub-type and to suggest options for targeted therapy. In parallel, studies of circulating free DNA are used to track actionable somatic mutations and monitor the response to therapy, and sequential biopsies from patients with recurrent disease are analysed to examine clonal emergence and evolution. A network of four laboratories undertakes this work, linked to a portfolio of clinical trials for patients with newly diagnosed or recurrent disease, coordinated by the Southampton Clinical Trials Unit. Complex bioinformatics analysis is used to refine the classification of the diseases according to detailed biological understanding and its impact on pathological behaviour.

A targeted approach is now being applied in a new Cancer Research UK funded trial of first-line therapy, ACCEPT of which OMDC is leading on sample processing, sequencing & bioinformatic analysis.

Key Publications
Characterisation of the changing genomic landscape of metastatic melanoma using cell free DNA.

Cutts A, Venn O, Dilthey A, Gupta A, Vavoulis D, Dreau H, Middleton M, McVean G, Taylor JC, Schuh A.

NPJ Genom Med. 2017 Sep 4;2:25. doi: 10.1038/s41525-017-0030-7.

PMID: 29075515 Free PMC article.

Targeted Next-Generation Sequencing of Plasma DNA from Cancer Patients: Factors Influencing Consistency with Tumour DNA and Prospective Investigation of Its Utility for Diagnosis.

Kaisaki PJ, Cutts A, Popitsch N, Camps C, Pentony MM, Wilson G, Page S, Kaur K, Vavoulis D, Henderson S, Gupta A, Middleton MR, Karydis I, Talbot DC, Schuh A, Taylor JC.

PLoS One. 2016 Sep 14;11(9):e0162809. doi: 10.1371/journal.pone.0162809. eCollection 2016.

PMID: 27626278 Free PMC article.

A statistical approach for tracking clonal dynamics in cancer using longitudinal next-generation sequencing data.

Vavoulis DV, Cutts A, Taylor JC, Schuh A.

Bioinformatics. 2020 Jul 28:btaa672. doi: 10.1093/bioinformatics/btaa672. Online ahead of print.

PMID: 32722772

Clinical-grade validation of whole genome sequencing reveals robust detection of low-frequency variants and copy number alterations in CLL.

Klintman J, Barmpouti K, Knight SJL, Robbe P, Dreau H, Clifford R, Ridout K, Burns A, Timbs A, Bruce D, Antoniou P, Sosinsky A, Becq J, Bentley D, Hillmen P, Taylor JC, Caulfield M, Schuh AH.

Br J Haematol. 2018 Aug;182(3):412-417. doi: 10.1111/bjh.15406. Epub 2018 May 29.

PMID: 29808933

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing.

Schuh A, Dreau H, Knight SJL, Ridout K, Mizani T, Vavoulis D, Colling R, Antoniou P, Kvikstad EM, Pentony MM, Hamblin A, Protheroe A, Parton M, Shah KA, Orosz Z, Athanasou N, Hassan B, Flanagan AM, Ahmed A, Winter S, Harris A, Tomlinson I, Popitsch N, Church D, Taylor JC.

Cold Spring Harb Mol Case Stud. 2018 Apr 2;4(2):a002279. doi: 10.1101/mcs.a002279. Print 2018 Apr.

PMID: 29610388 Free PMC article.

Characterisation of the changing genomic landscape of metastatic melanoma using cell free DNA.

Cutts A, Venn O, Dilthey A, Gupta A, Vavoulis D, Dreau H, Middleton M, McVean G, Taylor JC, Schuh A.

NPJ Genom Med. 2017 Sep 4;2:25. doi: 10.1038/s41525-017-0030-7.

PMID: 29075515 Free PMC article.

Precision medicine for patients with lymphoma; the Bloodwise Precision Medicine for Aggressive Lymphomas (PMAL) consortium

Bridgin Merron, Shamim Kazmi-Stokes, Thomas Cummin, Sharon Barrans, Shamzah Araf, Koorosh Korfi, Laura D Lopez Pascua, Josh Caddy, Kelly Cozens, Francesco Cucco, Rahman Uddin, Chulin Sha, Reuben Tooze, Gareth Griffiths, Ming Qing Du, Cathy Burton, David Westhead, Jude Fitzgibbon, Anna Schuh, Andrew Davies, Peter Johnson

Clinical Medicine Mar 2019, 19 (Suppl 2) 100-101; DOI: 10.7861/clinmedicine.19-2-s100