Transcript NewGene Business Process - Northern England Strategic

Molecular profiling of colorectal
cancers
Dr Angela Silmon
12th September 2014
Colorectal NSSG Audit Day
Outline
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Brief introduction to NewGene
Personalised Medicine
Molecular testing in colorectal cancer
Horizon scanning
NewGene Ltd
A pioneer in developing, validating and
delivering molecular diagnostics using the
latest high throughput sequencing and
genotyping technologies
Technology platforms
Genotyping
• Sequenom MassARRAY 4
– MALDI TOF mass spectrometer
– Low cost
– Rapid turn around
– Targeted mutations
Sequenom Mass Array 4
SAP
clean
PCR
Extension
reaction
Resin
Spotting
MALDI TOF
Data
analysis
Detector
F
5’end
3’end
3’end
5’end
R
Time of flight
5800Da
extension into SNP site
5500Da
Laser
Allele 1
6100Da
Allele 2
Sequenom chip
Sequenom Mass Array 4
5500Da
7000Da
Wild type allele only
(TT)
7000Da
Wild type and
mutant allele
present (TC)
7000Da
Mutant allele only (CC)
Personalised medicine portfolio
Gene
Mutations
Non-small cell lung
cancer
EGFR
17 point mutations
Indels exon 19 and 20
Inclds T790M
Metastatic colorectal
cancer
KRAS, BRAF, NRAS
23 mutations in each RAS gene
Inclds BRAF V600E
Melanoma
BRAF
GIST
cKIT, PDGFRA
Two step process
Funding
Gene
Mutations
EGFR
Astra Zeneca until Oct 2010
CCGs
ALK*
Pfizer
2015, likely change
Metastatic colorectal
cancer
KRAS, BRAF, NRAS
Merck Serono until May 2014
NHS England
Melanoma
BRAF
Roche
2015, TBD
GIST
cKIT, PDGFRA
Referring Trust
Non-small cell lung
cancer
* IHC carried out at Cellular Pathology, RVI, FISH test carried out by Cytogenetics
Referral pathway
Request CDF number
Refer for testing incld
CDF number
Automatic unregistration from CDF
T176
Refer for testing
Check T176 box
Test result
Test result
Therapy decision
CDF number if req
Funding: CDF
Therapy decision
Funding: NHS
England
Molecular testing in mCRC
• Mutation in the RAS genes offer prognostic value with
patients with a mutation in the KRAS or NRAS gene
having lower overall survival rates compared to wild
type
• Mutations predict lack of benefit from EGFR targeted
therapies such as Cetuximab and Panitumumab
• Mutations in codons 12 and 13 of KRAS most common,
~40% of mCRC patients
• Mutations in RAS genes found in ~ 50% of patients
Association of Clinical Pathologists Molecular
Pathology and Diagnostics Group
• Targeted mutations
– KRAS codons 12, 13, 59, 61, 117 and 146
– NRAS codons 12, 13, 59 and 61
• Interpretation
– Therapy license - wild type RAS genes only
– BRAF prognostic indicator but guidelines may
change
Wong NACS, Gonzalez D, Salto-Tellez M, et al. J Clin Pathol 2014
Association of Clinical Pathologists Molecular
Pathology and Diagnostics Group
• Primary or metastatic CRC tissue can be used
• Biopsy or resection specimen tissue can be
used
• The minimum neoplastic cell content tested
should be at least two times the assay’s LOD.
• Audit
– TAT ≤7 working days for >90% of samples
– Incident rates
– Failure rates
Wong NACS, Gonzalez D, Salto-Tellez M, et al. J Clin Pathol 2014
NewGene Audit 2014
• Turn around time
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• Failure rate
Target 5 working days
– < 1%
Range 2 - 11 days
• EQA
Average 3.4 days
– Participation since 2010
90% of reports issued within
– All genotyping maximum
5d
marks, no poor performance
• Incidence rate
Wild type samples 42%
Mutation positive samples 58%
Gene
NewGene
Reported
KRAS
42.7%
40%
NRAS
6%
5%
BRAF
9.3%
10%
Jan – June 2014
N = 500
Horizon scanning
• Require a comprehensive joined up
approach to molecular testing
– Funding mechanism
– Testing mechanism
Gene
Horizon
Non-small cell lung
cancer
EGFR
KRAS
Metastatic colorectal
cancer
KRAS, BRAF, NRAS
Melanoma
BRAF
NRAS
Horizon scanning
• OncoFocus
– Comprehensive test for actionable mutations
• UltraSeek
– Circulating tumour DNA
– 1% tumour content
GeneAA
ABL1
AKT1
ALK
BRAF
EGFR
FLT
IDH1
IDH2
JAK2
KRAS
NRAS
PIK3CA
T3151
E17K
F1174L
V600E, V600K, V600R
G719S, T790M, L861Q, E746A750del
1836del
R132H
R140Q, R172K
V617F
G12A, G12D, G12V, G12C,
G12S, G13D
Q61K, Q61R
E545K, E542K, H1047R
Horizon scanning
• Pilot data generation
– OncoFocus
– UltraSeek
– Business case for service delivery
– Phase I Clinical trials
– Clinical implementation
Thank you
Contact:
[email protected]
0191 242 1923
www.newgene.org.uk