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Cracking the code:
delivering a world first in genomicsChair: Professor Sir Malcolm Grant CBE
Professor Dame Sue Hill
Dr Nirupa Murugaesu
Professor John Mattick
Richard Erwin
Delivering the genomic revolution in today’s clinical care
Professor Dame Sue Hill @CSOsue
Chief Scientific Officer for England
SRO Genomics, NHS EnglandSeptember 2018
Genomics throughout the life of the NHS
• 60-year history of harnessing genomics & genetics – always been responsive to change
• Initially started with rare & heritable disease, then in cancer (all cancer is a genetic disease)
• Services rapid adopters of technology, most recently in the 100,000 Genomes Projectwhich established pathways for genomic medicine
• Provides platform to incorporate genomics across clinical care and deliver improved, personalised treatments
Disruption through the pace & price of technology
• Recent years have seen a step-change in the power & potential of genomics
• Exemplified by advances in the speed, price and availability of Whole Genome Sequencing+ computer power to analyse data
• Fast evolution of genomics is now tipping into disruptive revolution, opening up an explosion of possibilities
• Delivering more precise diagnoses & personalised care + more significantly, a new generation of predictive & preventative healthcare approaches
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Putting potential into practice - and driving the development of new treatment
• The NHS is delivering the genomic revolution now - new NHS Genomic Medicine Service rolled out from October
• Provides improved access to all genomic technologies (inc WGS) – particularly for cancer diagnosis and treatment – as well as rapidly driving the innovation pathway
• Every patient receiving a genomic test will get the opportunity to participate in research & innovation – benefitting individuals by opening up clinical trials & new treatments– benefitting the NHS by building evidence base & experience
• This national genomic data resource, will speed treatment development by partnering the NHS’s real world data and evidence with researchers & industry collaborators
Making genomics the day-to-day business of the NHS
Current focus: consolidating key services & infrastructure – for standardisation & efficiency
Establishing & embedding pathways to drive genomic mainstreaming across all clinical specialties(inc primary care)
Need change across the whole workforce – ongoing over next 10-20 years – to deliver the full potential of the technology (Topol Review)
NHS Long Term Plan provides opportunities to
consider the contribution genomics can make to
improving patient outcomes & experience
Fundamental interrelationship with medicines
- in optimisation & reducing ADRs but
- in understanding & determining ideal cohorts
for clinical effectiveness & future discovery
Future driven by real world data
- the true value proposition achieved through
strong partnerships with academia, industry,
international collaborators & involved patients
Delivering long-term value for NHS services
A focus on predictive & preventative healthcare
Supporting research & innovation
Improving patient care
VALUE
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100,000 Genomes Project:Clinical Impact
Nirupa Murugaesu
Consultant Medical Oncologist at St George’s Hospital, South London GMC
Clinical Lead for Molecular Oncology at Genomics England
Health and Care Innovation Expo
6 Sept 2018
Identification of somatic small variants in 136 potentially actionable genes across all solid tumours (n=5700)
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0
200
400
600
800
1000
1200
1400
No
. of
pat
ien
ts
Tumour Type
Small variants identified in known actionable genes
Small variants identified in potentially actionable genes
No small variants identified in potentially actionable geneso actionable variants
50% of 5700 patients have a
known actionable or
potentially actionable gene
identified
Molecular target → Targeted therapy
Pan genomic markers
- Mutational Tumour Burden
- Mismatch repair (MMR) genomic signatures(problem with DNA mismatch repair machinery)
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MMR deficient MMR proficient
Pan genomic markers
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High Mutational Tumour Burden
Higher tumour immunogenicity
Greater anti-tumour response to
immunotherapies
0
200
400
600
800
1000
1200
1400
Breast Colorectal Lung Renal Endometrial Ovarian
No
. of
pat
ien
ts
Tumour type for which there are clinical trials with dMMR/MTB as a biomarker
Low MTB High MTB (>10 coding SNVs per Mb)
Colorectal Case – 42 year old male
▪ Weight loss and jaundice
▪ Abdominal US
– 18cm liver lesion
▪ CT
– Circumferential sigmoid thickening
– Liver lesion
▪ Sigmoid biopsy
– Moderately differentiated adenocarcinoma
– NewGene mutation testing
• KRAS WT
• NRAS c.175G>A mutation
• BRAF WT
– MSI/MMR not done on diagnostic sample
– Fresh frozen sample sent for 100,000 Genomes Project
▪ Received 6 cycles FOLFIRI Chemotherapy
– Outcome: rising CEA (tumour marker), enlarging liver lesion
Colorectal Cancer in a 42 year old
WGS report– 83 actionable (domain 1) genes
including:• NRAS c.175G>A
VAF 0.13
• KRAS c.38G>A VAF 0.11
– Germline MSH6 mutation• Problem with DNA mismatch
repair machinery
248 coding SNVs
per megabase
Immunotherapy and Genomics
Next steps
– Clinical Genetics referral
- Family testing
– Immunotherapy trials
Impact of WGS
IHC for Diagnosis
IHC for MMR
RAS mutational
testing
DPYD
deficiency testing?
WGS
Acknowledgements
16
• St George’s Hospital 100,000 Genomes Project Cancer Team
Alison Berner
Ruth Pettengell
Katie Snape
Helen Hanson
John Short
George Morrissey
Tracy Odigie
Glen Brice
Mary Brice
Uzma Khan
Iulia Munteanu
Rahul Kurup
Keith Rogerson
• Genomics England
• Cancer Team
• Bioinformatics Team
• Informatics Team
• Clinical Data Team
• GeCIPs
• NHS England
• NHS Genomic Medicine Centres
• Health Education England
• Cancer Working Group
• Validation & Feedback Working Group
• Illumina/R&D Team
Professor John Mattick
CEO, Genomics England
Transforming healthcare in the UK:World leading partnerships
Richard ErwinManaging Director, Roche Products Limited UK
RXUKNATP00016g prepared August 2018
FutureNext generation RWDLinked data from genomics, integrated with clinical outcomes from real world settings
PresentAggregated trials and unlocking RWD
PastClinical trials
Unlocking the potential of personalised medicine
Genomics
EMR / RWD
Digital health
Advanced imaging
Digital pathology
Deep and broad data from
multiple sources... giving a high res view
of each patient and their disease
Our work in the UK
A shared vision for the future of genomics in the NHS
Doing now what patients need nextDoing now what patients need next
