1. Trends in Genetic Testing
Patrick Willems
GENDIA
Antwerp, Belgium

2. or Disclosure CEO and shareholder of GENDIA
(private lab offering genetic tests)
NO financial relationship with research bodies, medical
or pharmaceutical companies, hospitals or government or

3. Trends in Genetic Testing
1. From testing in university genetic labs
to testing in private medical labs
2. From patient testing
towards population screening

4. Current Organisation Genetic testing
Small local labs : small portfolio of tests ( < 50)
Same spectrum of tests : common + easy tests
Majority academic labs : research -diagnostic setting

5. Future Organisation Genetic testing
From small university genetic labs to :
1. Large private genetic labs
2. Large private medical labs

6. Trends in Genetic Testing
From small university genetic labs to :
1. Large private genetic labs
Prenatal testing : NIPT : Ariosa, Natera, Illumina, BGI
Carrier testing : Counsyl
Cancer testing : Germline risk test : Color, Myriad
Liquid biopsy : Pathway Genomics
2. Large private medical labs
Quest (Athena Genetics, Genzyme)
Labcorp (Correlagen)
Bioreference (GenedX)
Sonic
Eurofins (Emory Genetics)

8. GENDIA Network
1 Central lab
Test labs
Referral labs

9. GENDIA network

10. Advantages GENDIA network
1 lab to send samples to
1 lab to get results from
> genetic tests
Large portfolio
Easy selection of first test
Best Reflex testing

11. Trends in Genetic Testing
1. From testing in university genetic labs
to testing in private medical labs
2. From patient testing
towards population screening

12. From patient testing towards population screening
Form testing of 1 gene in 1 % of the population
suspected of a genetic disorder to :
whole genome testing of the whole population
to identify germline inherited mutations (WES/WGS)
2. Repeated screening for cancer DNA
to identify somatic non-inherited mutations (liquid biopsy)

13. Current paradigm Patient with suspected genetic disorder
visit
Pediatrician-neurologist-gynecologist
visit
Geneticist
Genetic test

14. Genetic screening test
Future paradigm
Healthy individual
visit
Physician
Dr. Google
Genetic screening test
visit
Physician
Geneticist
Dr. Google

15. 2. SOMATIC MUTATIONS IN CANCER
New genetic tests
GERMLINE MUTATIONS
NIPT
STID
CANCER RISK
WES / WGS
2. SOMATIC MUTATIONS IN CANCER
CT-DNA (liquid biopsy)

16. NIPT NON – INVASIVE PRENATAL TESTING
Prenatal testing of cff DNA (cell free fetal DNA)
from maternal blood for trisomy 21 (Down syndrome),
Trisomy 18, trisomy 13, and fetal sex
NIPT is worldwide the most frequent genetic test
with > 1 million tests per year (GENDIA : > NIPT)

17. NIPT cff DNA
<<< 1 % of total DNA in maternal circulation is fetal
% of cell-free DNA (cf DNA) in maternal circulation is fetal

18. NIPT NIPT currently is most common genetic test
More NIPTs than all other genetic tests together
Approximately 1 million NIPTs per year worldwide
Future Market value : 4 billion US / year
(price : 250 – 500 Euro per test)

19. STID SCREENING TEST for INHERITED DISEASE
Testing of future parents for common recessive diseases such as cystic fibrosis, thalassemia, fragile X, SMA (overall frequency : 1/200) before or during pregnancy CARRIER SCREENING is worldwide the second most frequent genetic test If both parents carry a mutation in the same gene the risk of an affected fetus is 25 % and prenatal testing by CVS or AC is offered

20. STID Cystic Fibrosis CFTR 1/3000 Spinal muscular atrophy SMN1 1/5000
Disorder
Gene
Frequency
Cystic Fibrosis
CFTR
1/3000
Spinal muscular atrophy
SMN1
1/5000
Deafness
GJB2
1/2000
Fragile X
FMR1
Thalassemia
HBB
1/3000 (1/300)
Many metabolic disorders
many genes
1/200

21. Genetic screening in Askhenazi jews

22. 2. SOMATIC MUTATIONS IN CANCER
New genetic tests
GERMLINE MUTATIONS
NIPT
STID
CANCER RISK
WES / WGS
2. SOMATIC MUTATIONS IN CANCER
CT-DNA (liquid biopsy)

23. CANCER RISK TESTING
The cancer risk test identifies patients with a germline mutation that have a high risk to develop cancer

24. Cancer tests Minority of cancers is inherited due to
germline mutations
CANCER RISK TEST
Majority of cancers is not inherited
and due to somatic mutations in the tumor
LIQUID BIOPSY

25. Inherited Cancer due to Germline mutations
Ovarian Cancer : 15 %
Breast Cancer : 10 %
Colon cancer : 5%
Prostate cancer : low
Lung cancer : very low

26. Cancer risk test Analysis of 30 cancer genes :
BRCA1, BRCA2, APC, ATM, BAP1, BARD1, BMPR1A, BRIP1,
CDH1, CDKN2A CDK4, CHEK2, EpCAM, GREM1, MITF,
MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLD1,
POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11 and TP53
Involved in genetic predisposition to
+ Breast and Ovarian cancer,
+ Intestinal and uterine,
+ Pancreas, stomach, skin and prostate cancer
Most likely third common test worldwide
Price : 359 Euro (10 Euro per gene)

27. CANCER RISK test GENE Breast Ovaria Uterus Colon BRCA1 ● BRCA2 MLH1
BRCA2
MLH1
MLH2
MSH6
PMS2
EPCAM
APC
MUTYH
MITF
BAP1
CDKN2A
CDK4
TP53
GENE
Breast
Ovaria
Uterus
Colon
TP53 ●
PTEN
STK11
CDH1
BMPR1A
SMAD4
GREM1
POLD1
POLE
PALB2
CHEK2
ATM
NBN
BARD1
BRIP1
RAD51C
RAD51D

28. WES (Whole Exome Sequencing) WGS (Whole Genome Sequencing)
WES / WGS
WES (Whole Exome Sequencing)
WGS (Whole Genome Sequencing)
To identify the genetic cause
of a presumed genetic anomaly

29. DNA Sequencing
> Radio - gel Fluorescent - capillary Next generation
Thousand bp / day Million bp / day Billion bp / day

30. Finding the one pathogenic variant that is the needle in the hay stack

31. The power of WES
CASE 1 : Recurrent attacks of metabolic acidosis, psychomotor retardation and microcephaly. Her metabolic profile was normal. Diagnosis unknown.
A pathogenic homozygous WDR73:c.287G>A variant was identified in exon 4 of the WDR73 gene.
Mutations in this gene lead to Galloway-Mowat syndrome.
In > 70 % of cases with presumed monogenic disease
the disease gene and mutation are identified by WES.
Price : 1500 Euro

32. WES / WGS 1. To identify the genetic cause of a congenital anomaly eci
2. To identify carriership for recessive disorders (expanded STID)
3. To identify monogenic mutations causing adult-onset disease
Neurological disease
Cardiovascular disease
Cancer
4. To identify risk factors for multifactorial disease

33. Trends in Genetic Testing
Patrick Willems
GENDIA
Antwerp, Belgium

34. 2. SOMATIC MUTATIONS IN CANCER
New genetic tests
GERMLINE MUTATIONS
NIPT
STID
CANCER RISK
WES / WGS
2. SOMATIC MUTATIONS IN CANCER
CT-DNA

35. CT DNA testing screens for somatic mutations in cell-free DNA (cf DNA)
CIRCULATING TUMOR DNA testing
screens for somatic mutations
in cell-free DNA (cf DNA)
from cancer cells in blood

36. CT DNA test : screening for germline mutations
CT DNA test screens Cell-free DNA from the cancer cells in blood (liquid biopsy)
DNA from cancer cells contains patient-specific oncogenic mutations
Cancer therapy is dependent upon the specific mutation (Personalised medicine)
Liquid biopsies are therefore “thera-diagnostic” tests
Estimated market of liquid biopsies : 40 billion USD per year

37. Targeted treatment for cancer
Personalised targeted treatment inhibits
specific mutations that cause cancer
These mutations are patient-specific
Mutations can be detected by molecular studies of :
. tumor material (biopsy) : FFPE, fresh or frozen
. blood (liquid biopsy)
Therapy is dependent upon the specific mutation
Personalised medicine

38. Advantages liquid biopsies
No tissue biopsy needed
No FFPE fixation
Profiling the overall genotype of cancer
primary cancer
circulating cells
metastases
Better evaluation of :
reaction to therapy
development of resistance
Also screening of patients without tumor but high cancer risk

39. Current indications for liquid biopsy
Follow up of patients with cancer
as a follow up of treatment treatment
Screening of individuals at high risk for cancer
(BRCA, HNPCC carriers)

40. Future indications for liquid biopsy
Every adult every year
as a general cancer screening

41. Looking into the future
NIPT
WGS
CT-DNA