Cancer Programme Update The 100,000 Genomes Project and Forwards

Transcription

1 Cancer Programme Update The 100,000 Genomes Project and Forwards Clare Turnbull Clinical Lead for Cancer Genomics, Genomics England Reader in Genomic Medicine, Institute of Cancer Research and Queen Mary University of London Honorary Consultant in Cancer Genetics, Guys and St Thomas NHS Trust ACGS Annual Meeting, Birmingham, June 26th 2017

2 To cover. Recruitment Sample Handling and Consensus statement Experimental work Haemato-oncology samples Return of results Germline Findings Genomics England Cancer Transition Group 10 July

3 Cancer Programme Phased roll-out Pilot Phase: 6 CRUK sites, 5 BRC sites Experimental Phase Gear 1 Gear 2 Gear 3 General recruitment Surgical resections (establish protocols) IIP Biopsies Focused cohorts (multiple samples in space and time) Individualised patient management (clinical turnaround time) 75x for tumour; 35x for germline ctdna pre-surgery Main Programme WAVE 1 WAVE 2 WAVE 3 Breast Renal Brain Prostate Sarcoma Upper GI Colorectal Germ Cell Tumours Ovarian Endometrial Lung Melanoma CLL Bladder Haem Onc 10 July

4 Recruitment

5 GMC self-reported recruitment to 2 nd June (including Pilot and IIP) 5,176 cancer samples (inc. tumour sample and germline) 4 weekly average = 110 samples 5

6 Number of participants registered per tumour type to 8 th June As of 4th May 2017 As of 8th June

7 Sample Handling

8 New FFPE guideline conditions (early 2016) GeL402 Fresh-Frozen GeL402 FFPE, new guidelines (NBF 80ºC) SUMMARY There are significant improvements with the new guidelines when compared to previous methods employing formal saline. However, data quality is still significantly worse than fresh-frozen (lower coverage uniformity and rate of somatic variant overcalling). ~ ~640,000 GeL402 FFPE, previous conditions (FS 80ºC) Confidential - Not for further distribution

9 Mutational burden in paired FFPE vs FF samples FFPE samples show increased mutational burden of small variants, both SNVs and indels This is an artefact of FFPE samples

10 Monitoring quality

11 Bench marking quality between centres

12 Bench marking quality between centres

13 Consensus Statement Detailed consent is still required to agree to the research aspects of the 100,000 Genomes Project and to state opinions on how a patient's germline findings should be handled. Implications of the Consensus Statement: 1.Laboratories which do not have a research HTA licence can still store tissue for the diagnostic arm of the 100,000 Genomes Project. 2.Samples can be handled in a genomic friendly way by not putting them into formalin as part of the diagnostic pathway without specific consent required to do this. 3.Consent for participation in the 100,000 Genomes Project can be taken after tissue has been sampled. 13

14 Number of Biopsies Proportion of biopsy/surgical resections St George s Hospital, South London GMC Number of FF samples collected (Biopsy vs Resection) September October November December January February March April May Joint Statement Implementation Resection Biopsy Number of biopsies as a proportion of total samples has been increasing After introduction of the Joint Statement biopsies accounted for 49% of samples in May 2017 The graph to the right provides a breakdown of biopsies by tumour type Biopsy numbers by tumour type Number of biopsies Breast Colorectal Bladder 14

15 Experimental Work

16 SOP development group Molecular Pathology Working Group: experiments, protocols, implementation GMC implementation group EXPERIMENTAL GROUP Q Initiation Implementation phase Q Main program up o gr t n e pm ol e v de P O S WS 1: upstream tumour handling WS 3: tumour assessment WS 5: DNA quantification and quality assessment WS 2: tumour processing, fixative, embedding WS 4: DNA extraction WS 6: Library preparation and sequencing *Led by Prof Louise Jones. Includes molecular pathology representation from BRC-GMC centres. Consultation with Joint Molecular Pathology Group

17 Alternative Freezing Strategies # Treatment (T:0 4h) Details 1 Liquid Nitrogen onto dry ice 2 Isopentane onto dry ice 3 Cryospray (indirect) onto dry ice 4 Cryospray (direct) onto dry ice Aim: To provide flexibility in freezing samples, particularly biopsies in clinic setting 5 Dry ice 6 Wet ice 7 Phosphate Buffered Saline 8 RPMI Culture Medium Storage at 4 C/RT Storage at 4 C/RT 1,1,1,2 tetrafluoroethane supplied in pressurised canister Widely used in pathology for rapid freezing for frozen section analysis Gives excellent morphology (for FF) 10 July

18 DNA Quality (Tapestation) cryospray cryospray Sample N2 N2 F1 A1 E1 B1 C1 D1 A2 E2 C2 B2 D2 S2 B3 A3 F3 DIN X X Confidential - Not for further distribution

19 RNA Quality

20 Alternative freezing: sequencing results No evidence of a negative impact of alternative freezing strategies % aligned reads Library insert size Coverage uniformity Numbers of somatic SV calls Somatic SNV number and distribution Number of small somatic variant calls and their distribution across repeat classes are similar in all conditions See example, right Confidential - Not for further distribution Data courtesy of Illumina

21 Paxgene: Alternative Fixatives PAXgene Tissue System Dual chamber system Tissue fixation Methanol based Tissue Stabiliser Requires formalin-free processing Morphology, IHC and ISH reported to be comparable to FFPE (Kap M et al. PLoS ONE 2011) 8 patients from 1 GMC PCR-based library prep for FFPE samples PCR-based library prep PAXgene samples PCR-free library prep for FF PCR-free library prep PAXgene samples Delta Cq values are good for all PAXgene samples; Delta Cq variable for FFPE Confidential - Not for further distribution Data courtesy of Illumina

22 Paxgene Sequencing QC runs PCR-free PAXgene libraries resemble FF most closely High-AT regions are under represented in FFPE; better with PAXgene High-GC regions are over represented with PAXgene (FFPE prep); FFPE samples are variable Confidential - Not for further distribution Data courtesy of Illumina

23 Full build data: (colorectal) purity estimate evenness score 39% 95.49% PAXgene PCR-free prep 21% 95.29% PAXgene PCR prep 48% 94.45% FFPE 45% 90.1% FF Confidential - Not for further distribution

24 PAX PCR-free PAX PCR-free PAX PCR-free PAX PCR-free Full build data: (colorectal) Somatic small variant distribution Somatic SNVs Somatic Indels Confidential - Not for further distribution Data courtesy of Illumina

25 Haemato-oncology

26 Haem-onc: Myeloid Disorders Disease Eligibility Criteria Tumour / Germline samples Additional samples High risk Myelodysplastic syndromes [MDS] / Acute myeloid Leukaemia [AML] Chronic Myeloid Leukaemia [CML] Unclassified Newly diagnosed (i.e. untreated): - MDS (blasts 10-19%) - AML (blasts >=20%) Extreme responders: - BCR-ABL transcript level using International Standards [IS] of <1% or >10% Patients who present in accelerated or blast phase (>10% blasts in PB or BMA) Patients present with cytogenetic abnormality in addition to t(9;22) Patients who progress after initial response: - Progress from chronic to accelerated / blast phase - BCR-ABL transcript level using IS reduced to <1% before increasing to >40% (on treatment) Difficult to define! But examples would include - Myelodysplastic/Myeloproliferative overlap syndromes [MDS/MPN} - Triple negative MPN - Others where mismatch between clinical diagnosis and pathological findings contact service desk if in doubt Tumour: DNA from pre-treatment peripheral blood [PB] / bone marrow aspirate [BMA] (2 ug / 500 ng) Germline intensive treatment: DNA from saliva taken at D5 of treatment (10 ug / 4 ug) Non-intensive treatment: DNA from cultured fibroblasts (10 ug / 4 ug) *alternative options being pursued Tumour: DNA from pre-treatment PB or BMA (2 ug / 500 ng) Germline: good responder: DNA from saliva at time BCR-ABL <1% (10 ug / 4 ug) All other categories: DNA from cultured fibroblasts (10 ug / 4 ug) *alternative options being pursued Tumour: DNA from pre-treatment PB or BMA (2 ug / 500 ng) Germline: DNA from cultured fibroblasts (10 ug / 4 ug) *alternative options being pursued Pre-treatment RNA (in form of GTC lysate) Pre-treatment RNA (in form of GTC lysate) Pre-treatment RNA (in form of GTC lysate) 26

27 Haem-onc: Lymphoid Disorders (1) Disease Eligibility Criteria Tumour / Germline samples Additional samples Chronic Lymphocytic Leukaemia [CLL] Myeloma - Any patient enrolled in FLAIR trial - Any untreated patient who has severe enough disease that they would meet the criteria for enrolment in the FLAIR trial and are fit enough for chemoimmunotherapy (including a purine analogue: either fludarabine or bendamustine) but have not been recruited to FLAIR for logistical, medical (e.g. poor renal function), genomic (i.e. TP53 abnormality in >20% cells) or patient choice reasons Any newly diagnosed untreated myeloma patient from whom sufficient CD138+ cells can be isolated from the BMA to make the minimum purity (>40%) and DNA requirements (>=500 ng minimum) Tumour: DNA from pre-treatment PB if lymphocytosis >25x10 9 /L, DNA from pretreatment BMA if lymphocytosis <25x10 9 /L (2 ug / 500 ng) Germline: DNA from saliva taken at a time when PB lymphocytosis is lymphocytosis <25x10 9 /L (10 ug / 4 ug) Tumour: DNA from pre-treatment CD138+ selected cells (e.g. post-column enrichment) aiming for purity >80% but will consider >40% if enrichment step undertaken (2 ug / 500 ng) Germline: DNA from PB or saliva (10 ug / 4 ug) Pre-treatment RNA (in form of GTC lysate) Baseline plasma for ctdna Follow up plasma for ctdna taken at 3/12 intervals for year 1, 6/12 intervals for year 2, time of any relapse Pre-treatment RNA (in form of GTC lysate) High grade lymphoma - Any newly diagnosed, untreated high grade lymphoma including )but not limited to): Diffuse Large B cell Lymphoma, Burkitt s lymphoma, Primary mediastinal B cell lymphoma, T cell lymphomas, Lymphoblastic lymphoma High grade lymphomas NOS - High grade [HG] transformation of a lower grade lymphoma or CLL Tumour: DNA from pre-treatment fresh frozen resection / biopsy with malignant cell percentage >=40% (2 ug / 500 ng) Germline: DNA from PB or saliva (10 ug / 4 ug) Pre-treatment RNA (in form of GTC lysate) Baseline plasma for ctdna Follow up plasma for ctdna taken at 3/12 intervals for year 1, 6/12 intervals for year 2, time of any relapse 27

28 Haem-onc: Lymphoid Disorders (2) Disease Eligibility Criteria Tumour / Germline samples Additional samples Paediatric Acute Lymphoblastic Leukaemia [ALL] Children & young adults (i.e. <25 years old at time of diagnosis) with ALL who have failed to obtain Minimal Residual Disease [MRD] levels of <5% at the D28 BMA Tumour: DNA from pre-treatment PB or BMA where blasts >=40% nucleated cells (NB will need to have DNA stored from diagnosis as will not know patient is eligible until post-d28 assessment (2 ug / 500 ng) Germline: DNA from saliva when there are no circulating blasts (morphological assessment of the peripheral blood) (10 ug / 4 ug) Pre-treatment RNA (in form of GTC lysate) 28

29 Returning Results

30 Preliminary analysis

31 Supplementary analysis Supplementary analysis Mutational signatures Structural variants Mutational density Coverage and copy number Mutation context Hypermutation rain plots

32 Cancer Analysis: Flow Main Programme (Fresh Frozen) 3,000 Cancer FF DNA Sample progress 2,500 2,511 2,000 1,687 1,500 1,000 1,276 1,194 Change to SRV Return of remaining 222 reports late June Samples at GMCs 2.1 Samples at Biobanks 2.2 DNA Dispatched to illumina 3.1 DNA passed QC 3.2 WGS Completed 4.1 WGS received by GEL 4.2 Ready for interpretation 6.1 Dispatched to GMCs Feedback received from GMCs

33 WGS with somatic small variants in 72 actionable genes Median 2.4 actionable genes across tumour types 33

34 Somatic small variants in 72 actionable genes across tumour types Breast Ovarian Colorectal Lung Renal Sarcoma Prostate Bladder 10 July

35 Cancer Analysis & Interpretation for Main Programme (for Fresh Frozen samples) 3,000 Cancer FF DNA Sample progress 2,500 2,511 2,000 1,687 1,500 1,000 1,276 1,194 Change to SRV Return of remaining 222 reports late June Samples at GMCs 2.1 Samples at Biobanks 2.2 DNA Dispatched to illumina 3.1 DNA passed QC 3.2 WGS Completed 4.1 WGS received by GEL 4.2 Ready for interpretation 6.1 Dispatched to GMCs Feedback received from GMCs

36 Interpretation in Cancer programme DNA Patient Tumour type NHS clinical team Validation Outcomes GeCIP(s) Gene Panels Report QC Reporting portal Genome sequence Annotated VCFs Gene Groups Variant filtering Variants Domains Clinical Review Knowledge Bases Annotation Providers

37 Illumina BaseSpace Variant Interpreter Associations Associations Column On/Off Tumor Type based on matching ontology term Four possible fields: Prediction: Based off ClinVar value and only possible with the Germline analysis Knowledge Base: only possible when in a workgroup BaseSpace Knowledge Network ClinVar Tiles indicate significance and number of entries: 3 7

38 Return of Germline findings

39 Proposal for expansion in return of germline variants Tier 1: high confidence pathogenic vars in gene set pertinent to tumour type susceptibility (current). Pre-annotation of pathogenic vars for childhood, Haem-Onc and other rare tumour types will be problematic?additional susceptibility variants?tier 2(OPTIONAL)*: (a) all (low freq) vars in gene set pertinent to tumour type susceptibility (b) all (low freq) vars in universal tumour type susceptibility gene set (~50 for adult solid tumours; many additional genes if expanding to haemonc and/or childhood)?addtional germline content to inform oncology management?tier 3(OPTIONAL)*: (a) all (low freq) vars in universal gene set relevant to therapy (DNA repair: HRD and BER genes) (b) all (low freq) vars in universal cancer gene set (eg cancer gene census; 572) To annotate germline var if var present in same gene or deletion spanning gene (LOH) on subtracted somatic analysis. * for local review. Molecular pathology lab receiving cancer reports should agree approach to analysis and management of these data with their molecular genetics laboratory and clinical cancer genetics service.

40 Pertinent Findings: genes Tumour Type Genes analysed Breast cancer BRCA1, BRCA2, PALB2, PTEN, TP53 Colorectal cancer MLH1, MSH2, MSH6, MUTYH (bi), PMS2, POLD1, POLE, PTEN, SMAD4, STK11 Ovarian cancer BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, RAD51C, RAD51D Prostate cancer BRCA2 Renal Cancer FH, FLCN, PTEN, SDHB, VHL, MET Sarcoma TP53 Melanoma BAP1, (CDK4), CDKN2A Endometrial cancer FH, MLH1, MSH2, MSH6, PMS2, PTEN Adult Glioma APC, ATM (bi), MLH1, MSH2, MSH6, PMS2, TP53 Upper GI MLH1, MSH2, MSH6, PMS2 40

41 Proposal for expansion in return of germline variants Tier 1: high confidence pathogenic vars in gene set pertinent to tumour type susceptibility (current). Pre-annotation of pathogenic vars for childhood, Haem-Onc and other rare tumour types will be problematic?additional susceptibility variants?tier 2(OPTIONAL)*: (a) all (low freq) vars in gene set pertinent to tumour type susceptibility (b) all (low freq) vars in universal tumour type susceptibility gene set (~50 for adult solid tumours; many additional genes if expanding to haemonc and/or childhood)?addtional germline content to inform oncology management?tier 3(OPTIONAL)*: (a) all (low freq) vars in universal gene set relevant to therapy (DNA repair: HRD and BER genes) (b) all (low freq) vars in universal cancer gene set (eg cancer gene census; 572) To annotate germline var if var present in same gene or deletion spanning gene (LOH) on subtracted somatic analysis. * for local review. Molecular pathology lab receiving cancer reports should agree approach to analysis and management of these data with their molecular genetics laboratory and clinical cancer genetics service.

42 NHSE Cancer Transition Working Group

43 The molecular context: a dynamic field Single gene/ Standalone test Small panel (eg hot spot Amplicon ) Genome Test required Number of markers Complexity of markers Larger generic panel (eg Hybridisationcapture) Bespoke, customdesigned tumourspecific panel Other nongenetic tests Technology Cost (for depth) Chemistry/Performance TAT Whole genome sequencing: a dynamic value proposition for each tumour context

44 The clinical context: a dynamic field When do we undertake molecular testing on patients? diagnostic biopsy surgery Biopsy (diagnostic/recurrence) +/-biopsy +/-biopsy LOCAL/REGIONAL DISEASE METASTATIC DISEASE neoadjuvant chemo-radiorx Adjuvant chemo-radiorx chemo-rx targeted drug chemo-rx Phase II/III Clinical trial Phase I clinical trial/ Experimental/compassi onate use drug Why do we undertake molecular testing on patients? Standard Care Diagnostic Prognostic Monitoring Targeted Drugs Clinical Trials Single new agent vs SOC Multi-arm umbrella/basket Molecular genomics-drug matching Discovery Research Longitudinal patient studies

45 Principles of evaluation capture CLINICAL; by tumour type Which genes have clinical utility for testing? What type of molecular markers in that gene? Type of actionability? Predictive, prognostic What is the level of evidence and impact: clinical (NHS) or research How widely is test implemented in NHS at the moment? LABORATORY; global What is the sensitivity of different standalone tests/ngs approaches in testing for each type of molecular marker? How well does that test/ngs approach perform wrt important metrics? Failure rate, TAT, DNA req, tolerance for DNA quality etc CLINICAL-LABORATORY; integrated; by tumour type What is the total palette of markers undertaken for that tumour type? For standard of care clinically? If we also think about entry to clinical trials/research? How well can different NGS-based approaches (panels, genomes) better deliver the palette of markers? Are standalone tests still needed? What are the INDIRECT IMPACTS of each approach (eg molecular pathology, complexity of laboratory workflow, ongoing requirement for redevelopment and redesign) CLINICAL-LABORATORY-ECONOMIC; integrated; by tumour type What is the costing for the different approaches IMMEDIATE COSTS: reagents, labcoats (INDIRECT IMPACTS: (re) development, molecular pathology) ADDITIONAL NON-LAB COSTS: data storage etc 45

46 Tumour Type experts consulted Sought input from >1 tumour type expert Tumour type Experts approached AML Anna Schuh, Angela Hamblin, Shirley Henderson Haem onc other Anna Schuh, Angela Hamblin, Shirley Henderson Sarcoma Nischalan Pillay, Adrienne Flanagan Breast Nick Turner+ NCRI clin studies group Ian Tomlinson, Gary Middleton, Phil Quirke, Nirupa Colorectal Murugaesu Ovarian James Brenton, Iain McNneish Prostate Johann De Bono, Mark Linch Crispin Hiley (cc Charlie Swanton), Andrew Hudson, Lung Gary Middleton, Nirupa Murugaesu Renal James Larkin, Samra Turajlic Brain Ashkan Keyoumars, Richard Houlston Endometrial David Church Bladder Simon Crabb John Bridgewater, Tim Meyer, Jeff Evans, Chrissie Upper GI Thirlwell Melanoma Paul Lorigan, James Larkin Childhood 46

47 40 different marker tests, 16 in standard of care testing

48 Laboratory Evaluation Gene molecular marker profile Scoring Stand alone tests Single fragment molecular marker test (e.g cobas, pyrosequencing) FISH karyotype Full gene screen (eg sanger of multiple fragments) MLPA/dosage analysis Single mutation(snv, small indel) o 3 NS NS 2 NS Oligo hot spots in same gene 3:excellent (FP and FN rate <1%, 3 NS NS 2 NS All disparate mutations across a gendetection >95% for VRF<5%) NS NS NS 2 NS Suitability/ CNV/amplification/loss 2: good (acceptable) NS 1 NS NS 2 sensitivity SV with known partner 1: poor NS NS SV with mutiple partner 0/NS: technology not suitable NS NS SV with any partner NS NS 2 NS NS Mutational signature NS NS NS NS NS High (tally score 5) DNA requirements (amount) Medium (tally score 3) Low (tally score 1) Low Medium High medium Medium tolerance of test to low quality DNA (ieffpe) 3: Good performance using poor quality DNA (ie FFPE) 2: Acceptable performance using poor quality DNA 1: Equivoval performance using 3 poor quality DNA: high quality DNA 2 NS 2 2 preferable 0: high quality DNA essential N/A: liquid tumour Needs live cells Typical TAT Failure rate 3: not required 0: required N/A: solid tumour 3: <3 days 2: <1 week 1: < 2 weeks 0: >2 weeks 3: <1% 2: 1-5% 1: 5-20% 0: >20%

49 PANELS Suitability/ sensitivity DNA requirements (amount) Gene molecular marker profile Scoring Single mutation(snv, small indel) or h Oligo hot spots in same gene 3:excellent (FP and FN rate <1%, All disparate mutations across a genedetection >95% for VRF<5%) CNV/amplification/loss 2: good (acceptable) SV with known partner 1: poor SV with mutiple partner 0/NS: technology not suitable SV with any partner Mutational signature Very High (tally score 10) High (tally score 5) Medium (tally score 3) Low (tally score 1) NGS DNA Amplicon Hot spot panel ( 200x) NGS large gene panel (Capture, generic) eg Illumina 170 genes ( 200x) NGS bespoke specific panel ( 200x) WGS at (tumour ~75x) NS NS NS NS NS NS NS 2 3 NS WGS at (tumour ~150x) Low Medium High Very High Very High tolerance of test to low quality DNA (ieffpe) 3: Good performance using poor quality DNA (ie FFPE) 2: Acceptable performance using poor quality DNA 1: Equivoval performance using poor quality DNA: high quality DNA preferable 0: high quality DNA essential N/A: liquid tumour Needs live cells Typical TAT Failure rate 3: not required 0: required N/A: solid tumour 3: <3 days 2: <1 week 1: < 2 weeks 0: >2 weeks 3: <1% 2: 1-5% 1: 5-20% 0: >20% ?? 49

50 Clinical Laboratory Integrator Context: STEP 1: SUMMARY OF MOLECULAR MARKERS FROM CLINICAL EVALUATION Standard Clinical Care count (Standard sensitivity) count (High sensitivity) Single mutation(snv, small indel) or hotspot 6 1 Oligo hot spots in same gene 0 All disparate mutations across a gene 2 CNV/amplification/loss 0 SV with known partner 8 SV with mutiple partner 0 SV with any partner 0 Mutational signature 0 STEP 2: BRINGING TESTS TOGETHER AS 5 APPROACHES Additional stand-alone non-ngs tests Single fragment molecular marker test (e.g cobas, pyro, qpcr) Full gene screen (eg sanger of multiple fragments) MLPA/dosage analysis karyotype FISH Approach1: all standalone tests Approach 2: hotspot panel(+ additional tests) Approach 3: generic gene panel(+ additional tests) Approach 4: bespoke gene panel (+ additional tests) Approach 5: (+ additional tests) Approach 6: (+ additional tests) Count of additional tests required by this approach

51 Consultation meeting: 23 rd May 2017 Adrienne Flanagan Dr Pippa Corrie Lucy Side Andrew Protheroe Fiona Carragher Manuel Salto-Tellez Anna Schuh Fiona Lalloo Mark Davies Clare Verrill Gareth Thomas Martin Gore Crispin Hiley Harpeet Wasan Nick Turner Darren Hargrave Ian Chau Nischalan Pillay David Church Ian Lewis Peter Clark David Thomson Ian Tomlinson Prof Karin Oien Dion Morton Ian Walker Rachael Hough Dr Alison Birtle Jacquie Westwood Rachel Butler Dr Andrew Biankin James Brenton Richard Edmondson Dr Andrew Pettitt James Larkin Richard Stephens Dr Colin Watts Jane Moorhead Rory Harvey Dr Daniel Rea Jo Martin Sarah Coupland Dr Lee Jeys Johann Debono Simon Crabb Dr Matt Hatton John Bridgewater Tony Williams Dr Meriel Jenney John Radford Wailup Wong 51

52 Secondary phase of data collection Review of proposed marker set Numbers, subtypes, patient journey, emerging technologies/approaches Key molecular targets going into Phase 3 To return by 26/6/17 10 July

53 Acknowledgements PILOTS/EXPERIMENTS Lab Leads: Anna Schuh Shirley Henderson Gerry Thomas Adrienne Flannagan Andrew Wallace David Gonzalez de C James Brenton Francesca Ciccarelli Emily Shaw Louise Jones Clare Verrill Pauline Robbe Dimitris Vavoulis James Hadfield ILLUMINA R&D team: Mark Ross Jenn Becq Zoya Kingsbury Sean Humphray David Bentley CANCER WORKING GROUP Dion Morton (pan cancer) James Brenton (ovary) Charles Swanton (lung) Johann de Bono (prostate) Nick Turner (breast) Ian Tomlinson (colorectal) Adrienne Flanagan (sarcoma) Josef Vormoor (childhood) James Larkin (renal) Anna Schuh (haem-onc) Crispin Hiley Mark Linch Samra Turajlicy Nischalan Pillay David Gonzalez (Imperial GMC) Frank McCaughan (SL GMC) Paul Cane (SL GMC) Tim Helliwell (NWcoast GMC) John McGrath (Wessex GMC) John Radford (Manchester GMC) Sean Grimmond (ICGC) David Cameron (clinical trials) Ian Cree (RCPath) Rowena Sharpe (CRUK) VALIDATION, INTERPRETATION AND FEEDBACK WORKING GROUP David Gonzalez de Castro (ICR/RMH) Phil Bennet (UCL) Angela Hamblin (Oxford) Shirley Henderson (Oxford) Manuel Salto-Tellez (Belfast) Andrew Wallace (Manchester) Gert Attard (Imperial) Gary Middleton (Birmingham) Rachel Butler (Cardiff) GENOMICS ENGLAND CANCER TEAM Louise Jones Alice Tuff Lacey Nirupa Murugaesu Joanne Mason Clare Craig Jason Chattoo Kay Lawson Cristina Aguilera Shirley Henderson Amanda O Neill Angela Hamblin Nancy Horseman Alona Sosinsky James Hadfield Augusto Rendon James Peach Simon Thompson Mark Caulfield Tom Fowler

54 Following the #genomes100k Like the Genomics England page Follow Genomics England /sign-up

55 FF vs FFPE by GMC as of 6 th June March June June June FF FFPE 55