Projects CMDL are currently undertaking

Dr Jean Abraham, co-lead Personalised Breast Cancer Programme
Personalised Breast Cancer Programme

The Personalised Breast Cancer Programme (PBCP) is a pioneering Cambridge-based study which reads DNA and RNA information like a barcode to tailor treatment for breast cancer patients. Discovering which genetic mutations are causing each patient's breast cancer enables doctors to choose the best treatment for each patient, whether standard treatment, targeted therapies or new drugs in clinical trial.

The CMDL isolates DNA and RNA from fresh frozen tumour of all patients enrolled in the trial. We also isolate germline DNA from buffy coats of these patients. The isolated material is QC checked, quantitated and sent to Illumina for whole genome sequencing (WGS) (weekly). All actionable variants detected by WGS are further validated by CMDL’s 350 gene panel.  NGS assay is performed and results discussed in weekly MDTs for patient management. 

Basket of Baskets clinical trial

The CMDL is one of the core laboratories involved in Cancer Core Europe’s Basket of Baskets trial. This is a Phase II multicentre study to evaluate targeted agents in molecularly selected populations with advanced solid tumours.
• CMDL receives tumour (FFPE slides or fresh frozen tumour) and germline material (buffy coat) from 7 cancer centres in Europe.
• CMDL performs extraction of DNA, 350 gene library prep, NGS and bioinformatics analysis.
• CMDL transfers Sequencing results to Netherlands Cancer Institute.
• CMDL panel results appear on a Molecular Tumour Board Portal hosted by Karolinska Institute, Sweden which are then used by clinicians in a weekly multidisciplinary team meeting (MDT) to select patients for trial.
• CMDL’s scientific staff participate in data analysis, interpretation and classification of variants.
• Turnaround time from receipt of tumour material to data transfer: 3 weeks.

Dr James Brenton, co-lead Ovarian Cancer Programme
Circulating tumour DNA isolation and NGS

The Brenton lab, CRUK Cambridge Institute is involved in circulating tumour DNA isolation and NGS in ovarian and fallopian cancer Phase II Trials (PHL; Pisarro; OV04). The BPL isolates plasma from freshly collected blood specimens (EDTA) tubes. Frozen Plasma is transferred to CMDL for ctDNA extraction. The ctDNA quantitated and NGS sequencing is performed by Fluidigm Access Array amplicon (ovarian trials).

The Rosenfeld lab, CRUK Cambridge Institute and Massie lab, MRC Cancer Unit routinely perform ctDNA isolation in CMDL for their translation studies.

Dr Dan Hodson
Diffuse large B cell lymphoma (DIRECT study)

The aim of the DIRECT Study is to establish a robust platform to identify those patients with diffuse large B cell lymphoma (DLBCL) most suitable for novel agent clinical trials based upon genomic subtype and an integrated response evaluation determined early in first-line therapy. The study is establishing a robust molecular pipeline to assign a genomic subtype to patients undergoing treatment for high-grade B cell lymphoma based upon their mutation profile from either diagnostic biopsy or ctDNA.

The CMDL is currently validating a custom lymphoma panel to work on FFPE diagnostic biopsies and ctDNA isolated from DLBCL patients. The whole process from sample collection to bioinformatic analysis will be performed by CMDL staff.

Dr Vincent Gnanapragasam, co-lead Urological Malignancies Programme
Personalised Prostate Cancer Programme

The lab receives Fresh frozen or FFPE material from tumours of patients enrolled in this study. Matched germline and tumour sequencing is performed with the 350 gene panel. A complete report is generated elucidating SNVs, Structural variants and tumour mutation burden. CMDL staff participates in MDT to help discuss and interpret results for patient management.

Dr Bristi Basu, Principal Investigator, PRICKLE trial
Phase Two pancreatic cancer trials
For the PRICKLE and SIEGE Phase Two pancreatic cancer trials, the lab is involved in:
  • Extraction of ctDNA from Plasma Samples and analysis of TP53/KRAS mutations by Digital Droplet PCR. 
  • Analysis and Interpretation of results obtained. 
  • Correlation of droplet PCR results with NGS on fresh frozen tumour or FFPE material.

Staff

University of Cambridge
Department of Oncology
Cambridge University Hospitals NHS Foundation Trust
Department of Oncology, Department of Medical Genetics
University of Cambridge, Cambridge University Hospitals NHS Foundation Trust
Department of Oncology
University of Cambridge
Cancer Research UK Cambridge Institute, Department of Oncology
University of Cambridge
Department of Oncology
University of Cambridge, Cambridge University Hospitals NHS Foundation Trust
Department of Oncology
Cambridge University Hospitals NHS Foundation Trust
Department of Oncology
University of Cambridge
Department of Oncology
University of Cambridge
Department of Oncology
University of Cambridge
Department of Oncology
University of Cambridge
Department of Oncology