Transcript GMC_Haematological_Malignany_Website_Version

100,000 genomes project
and haematological
malignancy
Dr Andrew Mumford
Clinical Director
www.genomicseducation.hee.nhs.uk/news
West of England Genomics Medicine Centre
WEGMC Governance Structure
5
WEGMC objectives 2016-18
1. Enable access to 100,000 genomes project
for WoE patients.
Whole genome sequencing and ‘omics’ of
4,650 samples from patients and families
with rare diseases or cancer.
2. Integrate genomic medicine into
standard clinical care pathways.
Set up timescale
First RD
samples
10th June
Designation
as GMC
23rd Dec
Go-live
Cancer
(NBT) and
RD (UHB)
27th May
First cancer
sample
27th June
01/16
01/17
Launch event
Future programme
Week 21
152 RD samples
34 cancer samples
1. Who is eligible?
2. Why whole genome sequencing?
3. How does is work for solid cancers?
4. How could it work for haematological
malignancy?
1. . Who is eligible?
2. Why whole genome sequencing?
3. How does is work for solid cancers?
4. How could it work for haematological
malignancy?
100,000 genomes project includes
Cancer and Rare Diseases
Genome samples
Approved cancers October 2016
1. Ovarian cancer
2. Lung cancer
3. Prostate cancer
4. Colorectal cancer
5. Breast cancer
6. Sarcoma
7. Renal cancer
8. Melanoma
9. Upper gastrointestinal tumours
10.Testicular cancer
11.Childhood solid tumours
12.Adult brain tumours
13.Bladder cancer
14.Endometrial cancer
15. Haematological malignancy
1. Who is eligible?
2. Why whole genome sequencing?
3. How does is work for solid cancers?
4. How could it work for haematological
malignanacy?
Why whole genome sequencing ?
PLT 64
PLT 78
Case 1
PLT 45
MPV 10.1 fl
Candidate genes for genetic platelet
disorders
Next generation sequencing:
Bait library design
Next generation sequencing
•Coding sequence of selected genes: gene panels
•Coding sequence of all genes: whole exome
• While exome + regulatory regions: whole genome
Seelection of a candidate gene
PLT 64
CYCS
THC4
(OMIM #612004)
PLT 78
Case 1
PLT 45
MPV 10.1 fl
RUNX1
FT-PAML
(OMIM #601399)
Case 2
Whole genome sequencing of cancer tissue
1. Who is eligible?
2. Why whole genome sequencing?
3. How does is work for solid cancers?
4. How could it work for haemato-oncology?
Defining and testing enrolment process
Overview schematic for cancer pathway
…How it works
Key features of Preliminary report
• Domain 1: variants in ‘Actionable Genes’
– annotated for gene-level and variant level actionability
– variant level actionability hyper-linked to Genome Oncology
(MyCancerGenome.gov)
– good, contemporaneous UK clinical trials annotations
(ClinicalTrials.gov)
• Domain 2: variants in ‘Cancer-related Genes’
• QC metrics:
– per sample: % neoplastic cells (pathology), tumour purity
(sequence)
– per sequence: GL/tumour mapped reads, insert size, chimeric
reads, median coverage, ‘eveness’ of coverage
– per variant: VRF
1. Who is eligible?
2. Why whole genome sequencing?
3. How does is work for solid cancers?
4. How could it work for haematological
maliganancy?
Why haematological malignancy?
1. Fifth most common cancer in UK
2. Majority relapse, progress or therapy related morbidity
3. Molecular diagnostics to improve prognostic estimates and
direct targeted therapies already standard care
•
•
•
•
•
•
GeL Steering Committee approved HM Programme 2016
Proposal developed by HM GeCIP
Funding limited to 6,000 samples (3000 patients)
Low priority for single gene disorders eg MPD, CML
Low priority for lymphoma because practical issues of
collecting solid tissue
Initial proposal consultation and then modified
Stage 1 HM
CLL, AML, Myeloma
Enrolment alongside FLAIR, AML 18/19 and MUK9/10
1. CLL
Saliva and peripheral blood sent to GMC laboratory and UK CLL
BioBank
2. AML/Myeloma
Saliva and marrow sent to trial biobanks.
Marrow cell sorted and both sent back to GMC laboratory
100,000 genomes data collected from data submitted for trial
Results and clinical reports distributed by local GMCs
Stage 2 HM- Inclusion
1. Newly diagnosed aggressive B and T-cell NHL
DLBCL, Burkitt, Mediastinal B cell, high grade lymphoma NOS
1. New AML/MDS outside trial
2. New myeloma outside trial
3. Unclassified HM (eg MDS/MPD overlap, mismatch between
clinical and pathological diagnoses)
4. CML extreme responders (compete molecular remission or no
morphological response after 3 months TKI treatment
5. Children with ALL with MRD>5% at day 28
Current position
Stage 1 disorders
Agreements with Cardiff CTRU and ICR October 210
Adapt Informatics pathways October 31st
Recruitment start
CLL- Nov 15th
AML- Jan 31st
Myeloma- not specified
Stage 2 disorders
From November 15th as determined by GMC
Feedback?
1. Where are patients enrolling to FLAIR. AML18/19 and
MUK9/10 ?
2. How many ?
3. Can trails infrastructure be augmented for additional
workload
4. Who are clinical leads for stage 1 and stage 2 disorders?
http://www.wegmc.org/
38