Van criekinge 2017_11_13_rodebiotech

Lab for Bioinformatics and
computational genomics
25 “genome hackers”
mostly engineers (statistics)
42 scientists
technicians, geneticists, clinicians
>250 people
Hardware/software engineers,
mathematicians, molecular biologists
Prof. Dr. ir Wim Van Criekinge

©2016 All rights reserved
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Next Generation (Epi)genetic biomarkers
Chief Scientific Officer

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CLIA Lab US Service Lab EU

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Kanker Beter Opsporen
door
Kanker Beter te Begrijpen

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door

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Kanker is een ziekte van het genoom

The human genome comprises the information contained in
one set of human chromosomes which themselves contain
about 3 billion base pairs (bp) of DNA in 46 chromosomes (22
autosome pairs + 2 sex chromosomes). The total length of
DNA present in one adult human is calculated by the
multiplication of
(length of 1 bp)(number of bp per cell)(number of cells in the body)
(0.34 × 10-9 m)(6 × 109)(1013)
2.0 × 1013 meters
That is the equivalent of nearly 70 trips from the earth to
the sun and back.
Genetic code - DNA

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Cancer is impairing key pathways/modules/networks

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Importance of Epigenetics (I)
R & D
Allows to (re)use one genomes
for different purposes

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Importance of Epigenetics (II)
R & D
• Allows to (re)use one genomes for different purposes
• Allows to integrate intrinsic with environmental signals

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Importance of Epigenetics (III)
R & D
• Allows to (re)use one genomes for
different purposes
• Allows to integrate intrinsic with
environmental signals
• Epigenetics driving etiology of many
human diseases

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door

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PSA Screening
Impact on Mortality
Welch HG et al. N Engl J Med 2015;373:1685-1687.
Incidence of Metastatic Prostate Cancer
at Initial Diagnosis: 1975–2012

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25% Will receive a false-negative
result
15% Will suffer complications from
biopsy (e.g. bleeding, infections, etc.)
~
3% Will be hospitalized in 30 days
following biopsy
Biopsies are
Gold Standard for Cancer Detection
Gershman et al.; Eur Uro 2016
Loeb et al.; Eur Uro 2013
Loeb et al.; J Urol. 2011.

Sampling error, Needle Missed Mark
Negative Prostate Biopsy
Standard 12-core biopsy
TRUS Guided Prostate Biopsy
Elevated PSA, Abnormal DRE, Family History
Elevated Clinical Risk Factors
Patient Compliance, Infections,
Unnecessary Repeat Biopsy
43% have repeat biopsy
Welch HG et al:. J Natl Caner Inst 2007;99: 1395 – 400. Pinsky PF et al:. BJU International 99, no. 4 (April 2007): 775–779.
Unnecessary Repeat Biopsies
Fear of Undetected Prostate Cancer

How ConfirmMDx Works
ConfirmMDx detects an epigenetic field effect associated with the presence of cancer at the DNA level
Biopsy
Cancer
Field Effect
Henrique R, et al:,Mol Cancer Res 2006;4:1-8

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ConfirmMDx Clinical Validation
The Journal of Urology 2013
Epigenetic Multiplex DNA
Methylation Test
•GSTP1 – DNA detoxification
•APC – apoptosis
•RASSF1 – cell cycle regulation
The most significant independent
predictor of cancer detection on
repeat biopsy
90% NPV
Stewart GD et al; Journal of Urology 2013
MATLOC Study

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ConfirmMDx Positive Results
 Personalized risk assessment for likelihood of harboring
aggressive cancer
 Men who benefit from MRI/biopsy and early detection
ConfirmMDx Positive

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Methylation
Negative
Methylation
Positive
Low Risk
Active Follow Up
Negative
Prostate Biopsy
ConfirmMDx
High Risk
Repeat Biopsy
Routine
Screening
Risk Profile
Provides Personalized Risk Assessment
Patient Profile: Men being considered for repeat prostate biopsy
 96% NPV for Clinically Significant Cancer
 90% NPV for All Cancers
Van Neste et al; The Prostate 2016

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SelectMDx for Prostate Cancer
Clinical Validation of a Risk Profile for the Detection of High Grade Cancer
SelectMDx Risk Profile:
 Strongest predictor of high-grade disease
 98% NPV for GS ≥7 cancer
 AUC of 0.89 (95% CI 0.85-0.95)
European Urology 2016
Van Neste et al., European Urology 2016

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Collect First Void Urine in
Transport Medium
RNA Isolation
KLK3 RT-qPCRHOXC6 RT-qPCR
HOXC6/KLK3
DLX1 RT-qPCR
DLX1/KLK3
Cq-Values:
Ratios:
Score:
SelectMDx qPCR

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Elevated PSA Urologist DRE Urine
Urine test for the prediction of histopathological outcome of prostate biopsy
Non-invasive, Liquid Biopsy to Identify Patients for Prostate Biopsy
Follow-up
Discuss with
patient
MRi or Biopsy
routine PSA

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Patient Report
Sample
Improves the Identification of Men
for Prostate Biopsy:
High Risk
• Personalized risk profile
• Increased risk for aggressive cancer
• Men who may benefit from biopsy
Very Low Risk
• 98% NPV for GS ≥7 Disease
• May avoid biopsy
• Return to routine screening
Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer. Leyten et al. Clin Cancer Res, 2015

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Provides Patient’s Personalized Risk Profile
A patient at increased risk will receive a report which indicates his likelihood for
prostate cancer on biopsy and probability for aggressive disease

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Routine Screening
Elevated PSA,
Abnormal DRE
Very Low Risk
for GS ≥ 7 PCa
Consider
Biopsy or MRI
Increased Risk
for GS ≥ 7 PCa
99.6% NPV for GS ≥8
98% NPV for GS ≥7
Very Low Risk
Avoid Biopsy
For patients being considered for initial prostate biopsy
 Identify men at high risk for aggressive cancer
 Assay performed on non-invasive, urine sample
Improved Risk Stratification for
Clinically Significant Cancer

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AssureMDx for Bladder Cancer
Non-invasive, Liquid Biopsy to Identify Patients with Bladder Cancer
Patient
Blood in urine
Test
Runs on any open
PCR/Sequence instrument
Follow-up
Yes/No
CT scan or Cystoscopy
Result
Likely hood risk
score
Routine
monitoring

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Biomarkers Before Biopsies complements the ProstateMDx.org website

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Epigenetic Editing
Genome Hacking/(re)progamming

Van criekinge 2017_11_13_rodebiotech

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