Update on TP53 analysis accreditation project - ericll.org · E. Delabesse Toulouse, CHU M....
Transcript of Update on TP53 analysis accreditation project - ericll.org · E. Delabesse Toulouse, CHU M....
Update on TP53 analysis accreditation project
Sarka Pospisilova, Eugen Tausch,
Jitka Malcikova, Martin Fox and Stephan Stilgenbauer
For all laboratories performing the TP53 analysis in CLL - validate different
techniques on TP53 mutation analysis
Support introduction of TP53 analysis in labs with less experience
(to provide assurance of the results quality).
Discuss the problematic issues and give individual recommendations.
Improve analysis harmonization and interaction between centers.
Provide an official document on the quality control assessment.
Aims of the project
Participating Laboratories :
49 centers participated in the study and asked for samples
> 47 centers asked for gDNA
> 6 centers asked for RNA (and gDNA)
> 1 center asked for viable cells (not delivered)
39 centers delivered results within 3 months after sample arrival
3 centers notified not to able to perform analysis
3 centers (2x Russia, Venezuela) did not receive samples (logistic reasons)
4 centers did not reply to our reminders
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
Participating Labs (49) Applicant Center:
E. Eldering Amsterdam, Academic Medical Center P. Panayiotidis Athens, University of Athens
J. Nomdedeu Barcelona, Hospital de la Santa Creu i Sant Pau
M. Catherwood Belfast, Belfast City Hospital
F. Baran-Marszak Bobigny, Hopital Avicenne P. Piccaluga Bologna, University of Bologna
Sottini Brescia, lab. Biotecnologie
J. Malcikova Brno, University Hospital Brno D. Naguib Caen, CHU Côte de Nacre
L. Veronese/P. Combes Clermont Ferrand, CHU ESTAING I. Praulich/S. Prall Cologne, University at Cologne
L. Pedersen / C. Geisler Copenhagen, Rigshospitalet S. GIRAUDIER Créteil, Hopital Henri Mondor
M. McBean East Melbourne, Peter MacCallum Cancer Centre
J. Bryon Edgbaston, Birmingham Women's Hospital J. Lindgren Gothenburg, Sahlgrenska university Hospital
N. Halbsgut Göttingen, Klinik für Hämatologie und Onkologie T. Tadmor Haifa, Bnai Zion Medical Cenzer
N. von Neuhoff Hannover, Hannover Medical School
N. Bilous Kiev, Research Center for Radiation Medicine K. Filonenko Kyiv, National Cancer Insitute
S. Jayne Leicester, University of Leicester S. Franke/F. Lambert Liege, CHU Liege
K. Lin Liverpool, University of Liverpool, Sanger
Dr. Nicholas Lea London, Kings College Hospital
Applicant Center: Veronese Silvio Milano, Molecular Pathology Unit
Cristina Tresoldi Milano, Ospedale San Raffaele Andrey Sudarikov Moscow, National Hematology Center
Davide Rossi Novara, University of Eastern Piedmont Miss Helene DREAU Oxford, Oxford University Hospitals NHS Trust
Fred Davi Paris, Hopital Pitié-Salpêtrière Silvia ZIbellini Pavia, Fondazione IRCCS Policlinico San Matteo
Cristina Mecucci Perugia, University of Perugia
M. González, E. Sebastián Salamanca, University Hospital of Salamanca Dimovski Skopje, Faculty of Pharmacy
F. Forconi Southampton, University of Southampton Rumyanciev St. Petersburg, V.A.A. Federal Centre of Heart
A. N. Tran Stockholm , Karolinska University Hospital
U. Tostar Stockholm, Karolinska University Hospital, D. Wren/D. de Castro Sutton, The Royal Marsden NHS Foundation Trust
K. Stamatopoulos Thessaloniki, G. Papanicolaou Hospital A. Makris/ K. Stamatopoulos Thessaloniki, INAB-CERTH
S. Niki Thessaloniki, Papanikolaou Hospital
E. Delabesse Toulouse, CHU M. Hermanson Uppsala, Clinical Genetics
M. Hernandez Valencia, Universidad de Carabobo M. Fritzer-Szekeres/R. Ferdig
Sunder-Plassmann Vienna, Clinical Institute for Laboratory Medicine
E. Novella Vinzenca, S. Bortolo Hospital
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
Participating Labs
49 centers participated in the study and asked for samples
without result with result
BRNO ULM
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide
50 labs worldwide 49 labs in Europe* Sample shipping
Correspondence
Project work flow
Results
* and Australia and Venezuela
Online Survey Participation
Exon1 Exon2 Exon3 Exon4 Exon5 Exon6 Exon7 Exon8 Exon9 Exon10 Exon11
3 centers 2 centers
19 centers
5 centers 3 centers
8 centers
5 centers
45 labs
23 labs
45 labs
23 labs
IAR
C
4 5 6 7 8 9 10 11 3 2
40
cen
ters
21
cen
ters
N=2
87
17
Covered TP53 Exons in participating labs
3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
Sample 1
Sample 2
Sample 3
Sample 4
Sample 5
Disomic Somatic
Deleted
Somatic
Disomic Somatic
Disomic Somatic
Deleted
Somatic
FISH IARC
2
TP53 accreditation - Sample Selection
c.517G>T VF=47%
c.715A>G VF=44%
c.811G>T VF=41% c.370T>C VF=38%
c.1028delA VF=93%
Accreditation requirements - exon 4-9
3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
Sample 1
Sample 2
Sample 3
Sample 4
Sample 5
c.517G>T VF=47%
c.715A>G VF=44%
c.811G>T VF=41% c.370T>C VF=38%
2
Accreditation Requirements
WT
Mutated
Mutated
Mutated
Mutated
Result
c.517G>T VF=47%
c.715A>G VF=44%
c.811G>T VF=41% c.370T>C VF=38%
c.1028delA VF=93%
3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
2 3 4 5 6 7 8 9 10 11
Sample 1
Sample 2
Sample 3
Sample 4
Sample 5
2
Accreditation requirements - exon 4-10 Accreditation Requirements
WT
Mutated
Mutated
Mutated
Mutated
Result
c.1028delA VF=93%
c.517G>T VF=47%
c.715A>G VF=44%
c.811G>T VF=41% c.370T>C VF=38%
Results of sample analysis
80%
8%
6%
6%
Not able to send results
(4)
No answer (3)
No sample received (3)
Results provided
failed Exons 4-9
n=49 n=39 (34 succeeded, 5 failed)
Exons 4-10
<28d
>28d >28d
<28d
single
single
<28d
>28d *
*
*
*
0
5
10
15
20
25
<28d >28d: 3
<28d: 8
>28d
* Only 1 of 2 mutations in sample 4 detected
n=23
n=11
Minimal requirements
Validate sample 2-4 as mutated and sample 1 as unmutated.
Perform analysis within 3 months after sample receipt.
Good laboratory practice
Detect all mutations in samples 2-5.
Finish analysis and confirmation assay within 28 days.
Provide a clinical report including minimal required informations.
Accreditation requirements
Centers with successful TP53 mutation analysis
Applicant Center: F. Baran-Marszak Bobigny, Hopital Avicenne
P. Piccaluga Bologna, University of Bologna Sottini Brescia, lab. Biotecnologie
J. Malcikova Brno, University Hospital Brno
L. Veronese/P. Combes Clermont Ferrand, CHU ESTAING I. Praulich/S. Prall Cologne, University at Cologne
L. Pedersen / C. Geisler Copenhagen, Rigshospitalet S Giraudier Créteil, Hopital Henri Mondor
M. McBean East Melbourne, Peter MacCallum Cancer Centre J. Bryon Birmingham Women's Hospital
N. Halbsgut Göttingen, Klinik für Hämatologie und Onkologie
N. von Neuhoff Hannover, Hannover Medical School N. Bilous Kiev, Research Center for Radiation Medicine
S. Jayne Leicester, University of Leicester K. Lin Liverpool, University of Liverpool, Sanger
M. McBean Melbourne, PeterMac
Veronese Silvio Milano, Molecular Pathology Unit
Applicant Center: Cristina Tresoldi Milano, Ospedale San Raffaele
Davide Rossi Novara, University of Eastern Piedmont Miss Helene DREAU Oxford, Oxford University Hospitals NHS Trust
Silvia ZIbellini Pavia, Fondazione IRCCS Policlinico San Matteo
Cristina Mecucci Perugia, University of Perugia M. González, E. Sebastián Salamanca, University Hospital of Salamanca
Dimovski Skopje, Faculty of Pharmacy
A. N. Tran Stockholm, Karolinska University Hospital
U. Tostar Stockholm, Karolinska University Hospital D. Wren/D. de Castro Sutton, The Royal Marsden NHS Foundation Trust
K. Stamatopoulos Thessaloniki, G. Papanicolaou Hospital A. Makris/ K. Stamatopoulos Thessaloniki, INAB-CERTH
N. Stovroyianni Thessaloniki, Papanikolaou Hospital
E. Delabesse Toulouse, CHU M. Hermanson Uppsala, Clinical Genetics
Sunder-Plassmann Vienna, Clinical Institute for Laboratory Medicine
E. Novella Vinzenca, S. Bortolo Hospital
Reports Lab name
Type of analysis
Result & Interpretation
Date of sample acquisition
Patient Identifier
Type of material and technique
Responsible Person
Next Steps
Brief report of survey and analysis results
Contact each lab with individual feedback / specific recommendations
ERIC Certificate to 34 successfull participants
Initiation of annual sample exchange for re-accreditation
Sample exchange for NGS based analysis
TP53 analysis technique harmonization approach