Genomic Medicine Centre Overview Dr Andrew Mumford - Clinical Director Axel Walther – Clinical Lead for Cancer Catherine Carpenter-Clawson – Programme Manager Amanda Pichini - Lead Genomic Practitioner

NHS Genomic Medicine Centres and the 100,000 Genomes Project Dec 2012: PM David Cameron launches project to sequence 100,000 Genomes from NHS patients with cancer and rare disease to cement UK as a world-leader in Genomic Medicine For cancer patients both their own genome and the tumour genome will be sequenced Dec 2014: NHS England establishes first NHS Genomic Medicine Centres to coordinate activity across populations of ~5 million, working to common protocols & specification to ensure comparability and quality of data NHS GMCs work as network model with Lead Organisation working in partnership with other trusts as Local Delivery Partners 2015: Experimental cancer pathway develops early protocols 2015: Cancer initiation phase starts, with experimental work to determine effectiveness of protocols Feb 2016: Cancer Main Programme live in 12 centres, with phased roll-out

100,000 Genomes project and genomic medicine Initiative to perform WGS on 100,000 samples from English NHS patients Make ‘genomic medicine’ part of standard care Diagnosis Prognosis Personalised treatment

Types of NGS Tests Targeted Gene Panels (TGPs): Up to ~ 100 pre-selected genes based on a particular disease type. Whole Exome Sequencing (WES): sequencing of the “exome,” which includes all of the exons (DNA sequences within protein coding genes). The exome encompasses ~2% of all DNA Whole Genome Sequencing (WGS): sequencing of the entire genome, including coding and non-coding regions. TGPs may be useful for patients that have a relatively defined disease aetiology, for which there are known causative genes. Because this test is tailored to a particular phenotype, it does not include secondary findings (variants not related to the disease of interest). WES or WGS may be useful for patients with: Many possible diagnoses A complex phenotype that suggests a genetic aetiology but does not correspond to a known condition A condition with a likely genetic aetiology, but other targeted tests have failed to provide a diagnosis WES and WGS can reveal new disease-causing variants whose clinical significance in causing particular phenotypes was not previously known. However, unlike TGPs, WES and WGS may reveal secondary findings, as they encompass DNA sequences not related to the primary disease of interest. WES is less costly and easier to analyze than WGS; however, WGS may cover some parts of the exome better than WES because of its more comprehensive overall coverage of the genome.

Includes Cancer and Rare Diseases

Genome samples

Delivery of the 100,000 Genomes project 13

West of England Genomics Medicine Centre (WEGMC)

WEGMC programme 2016-17 Complete whole genome sequencing of 4,650 samples from patients and families. - Consented from now until Sept 2017 Integrate whole genome sequencing into standard clinical care pathways.

WEGMC structure

Cancer Recruitment to 100,000 Genomes Nationally Initiation Phase 567 samples achieved and move to main cancer programme earlier this year Initially 5 cancer types identified Breast Colorectal Lung Sarcoma Prostate Expected expansion from early May 2016 to further cancer sites (Brain, Skin, UGI, Testicular, Renal) Ongoing discussions regarding further expansion

WEGMC Programme for Cancer Decision made to take a phased/pilot approach to the programme for cancer Start consent and pathway work in NBT and breast cancer Good track record for ‘research activity’ Enthusiasm Close links with GMC laboratory teams Funding identified to support consent 0.5 Band 6 funding into entire ‘research team’ will support breast but also roll out to other teams

Proposed pathway

What next? What else do we need to consider? Appreciate your continued support and engagement. Any queries: Catherine Carpenter-Clawson Email: Catherine.Carpenter-Clawson@nbt.nhs.uk Tel: 07732 561067