Your Health Topic : Genomics and Clinical Practice How genetics is improving care for patients

Transcription

1 Your Health Topic : Genomics and Clinical Practice How genetics is improving care for patients

2 Speaker Dr Kevin Monahan FRCP PhD Consultant Gastroenterologist, Family History of Bowel Cancer Clinic, Chelsea & Westminster Hospitals NHS Trust & Honorary Senior Clinical Lecturer, Imperial College London

3 Introducing Genomics in Healthcare

4 Rosalind Franklin Born in Notting Hill in July 1920 Identified DNA double helix King s College London 1951 Lived at Drayton Gardens, Chelsea Died at only age 37 years in 1958 at RMH Cause of death: Ovarian cancer..due to BRCA gene mutation?

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7 Summary Genetics and Clinical Practice Rare Diseases Cancer Family History Clinic 100k Genomes Project

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17 The 100,000 Genomes Project High Level Timeline Routine Service

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22 Rare Diseases - WGS Severe intellectual disability occurs in 0.5% of newborns Whole-genome sequencing at 80x in 50 parent-offspring with no diagnosis for their severe intellectual disability Overall 62% increase in diagnostic yield with WGS Veltman et al Nature 2014

23 First families diagnosed from the Newcastle BioResource pilot 1. Leslie Hedley, 57 WGS revealed Mr Hedley s kidney failure was caused by a particular genetic variant (INF2 mutation). His family is also being tested and their blood pressure can now be effectively controlled by drugs available on the NHS. 2. William and Allan Carpenter aged 79 and 69 Suffered from muscle loss and weakness. They have now been diagnosed with inherited nerve damage, known as peripheral neuropathy. The brothers may be joining a treatment trial which, if successful, could prevent family members developing the same condition.

24 Two brothers: distal sensory-motor neuropathy Two brothers with a distal motor neuropathy Symptoms began in late 40s-early 50s progressed over years Currently aged 79 and 72 Remain ambulatory but with significant difficulties Whole Genome Sequence Expected pathogenic mutation in a transport gene for Serine Validation: Confirmed Opportunity: Potential for treatment trial with l-serine

25 Diagnostic Odyssey Distal sensory-motor neuropathy Additional investigations Nerve conduction studies (x 4) Total cost: 2905 (excluding routine biochemical investigations AND excluding costs of appointments)

26 "Insanity is repeating the same mistakes and expecting different results"

27 Cost of Genome sequencing

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31 BRAF inhibitors for Melanoma

32 Cancer Cancer is a disease of disordered genomes over 200 driver mutations/structural rearrangements recognised Molecular diagnostics stratified precision management Targeted drugs: subvert mechanism of mutant protein <20 mutations/svs routinely tested for: single gene/hot-spot sequencing/panels 50,000 WGS allocated to cancer programme Cancers currently included in 100KGP: Lung, breast, colon, prostate, ovary, Haematological malignancies (CLL) Renal, Sarcoma, Childhood Cancer of unknown primary Additional tumour types under review

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38 Inheritance, Carcinogens etc A B APC KRAS/BRAF C Hypo/hyper-methylation Loss 18q / P53 D

39 Aldred Warthin Family G Ann Int Med 1913

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41 Lynch Syndrome Amsterdam Criteria 3 FDRs with bowel cancer, 2 Generations, 1 Under age 50 years

42 Lynch Syndrome Family, MSH2 mutation

43 Epidemiology Population prevalence 1: % CRC 1200 CRC in UK annually 1200 other cancers Only 5% of LS patients known in UK Thanks to Ian Frayling; Yurgelun CGA 2016

44 Lynch Syndrome Management Colonoscopy: Every 2 years from age years Mean 7 years extra life Aspirin ~50% reduction of cancer risk Lifestyle Modification Prophylactic TAH-BSO ~age 40 CRC diagnosis Adaptive surgery Personalised onco-therapy

45 Stratified Care in Lynch Syndrome High quality colonoscopists Quality assured Timely recall Risk Stratified Lessons from BRCA?

46 35% of colorectal cancer due to hereditary causes Lichtenstein et al 2000, NEJM

47 Polyposis

48 Referral pathways CRC MDT Gynaecology GPs Hereditary CRC Service Clinical Genetics Endoscopy Colorectal/ Oncology OPD

49 Illumina Trusight panel Next generation sequencing platform 94 genes and 284 SNPs associated with a cancer predisposition

50 When Should You Be Referred? 1x Close relative <50 years 2x Close relatives at any age.

51 100K Genomes Project NHSE and GMCs GeCIPs Genomics England Illumina The Principal Partners HEE Commercial Partnerships

52 Genomics England Genomic Medicine Centres Announced December East of England NHS GMC Led by Cambridge University Hospitals NHS Foundation Trust; 2. South London NHS GMC Led by Guy s and St Thomas NHS Foundation Trust. 3. North West Coast NHS GMC Led by Liverpool Women s NHS Foundation Trust. 4. Greater Manchester NHS GMC Led by Central Manchester University Hospitals NHS Foundation Trust 5. University College London Partners NHS GMC Led by Great Ormond Street Hospital NHS Foundation Trust 6. North East and North Cumbria NHS GMC Led by The Newcastle upon Tyne Hospitals NHS Foundation Trust. 7. Oxford NHS GMC Led by Oxford University Hospitals Foundation Trust. 8. South West Peninsula NHS GMC Led by Royal Devon & Exeter NHS Foundation Trust. 9. Wessex NHS GMC. Led by University Hospital Southampton NHS Foundation Trust. 10.West London GMC. Imperial Chelsea Marsden Brompton 11.West Midlands NHS GMC. Led by University Hospitals Birmingham NHS Foundation Trust.

53 Education in Genomic Medicine MSc in Genomic Medicine CPD access to MSc modules for specialist practitioners Specialist Clinical workforce development in Genomic Medicine: specialist genetics, pathology and specialist clinical workforce Specialized scientific training: fellowships funded over 3/5 years: Molecular Pathology including Infections and Pathogens Genetics / genomics Bioinformatics Specialist on-line learning Bioinformatics workshops

54 Illumina: Delivering Sequencing at scale Sequencing Centre: Wellcome Trust awarded to establish NHS Genome Sequencing Centre ( 27m) at Hinxton Sequencing Centre - Hinxton

55 Opportunities Be at the international forefront of implementing the latest research evidence for patient benefit Position the hospital early in the developing specialist networks for exchanging clinical knowledge and sharing technology and resources Benefit from the UK Government s prime-funding into new technology Continue to attract patients and staff to a hospital known for innovative, highest standard practice