CERTIFIED CENTERS+
  • ARGENTINA
  • AUSTRALIA
  • AUSTRIA
  • BELGIUM
  • BRAZIL
  • BULGARIA
  • CANADA
  • CHINA
  • CROATIA
  • CYPRUS
  • CZECH REPUBLIC
  • DENMARK
  • ESTONIA
  • FINLAND
  • FRANCE
  • GERMANY
  • GREECE
  • HUNGARY
  • INDIA
  • IRELAND
  • ISRAEL
  • ITALY
  • JORDAN
  • LATVIA
  • LITHUANIA
  • MACEDONIA
  • MEXICO
  • NETHERLANDS
  • NORWAY
  • POLAND
  • PORTUGAL
  • QATAR
  • ROMANIA
  • RUSSIA
  • SLOVAKIA
  • SLOVENIA
  • SOUTH AFRICA
  • SPAIN
  • STATE OF PALESTINE
  • SWEDEN
  • SWITZERLAND
  • TURKEY
  • THE UNITED KINGDOM
BACKGROUND+

In chronic lymphocytic leukemia (CLL), TP53 gene aberrations due to chromosome 17p deletion ⌊del (17p)⌋ and/or TP53 gene mutation are associated with adverse prognosis and poor response to chemo (immuno) therapeutic regimens. Deletion and/or mutation of the TP53 gene occur on average in 10-15% of untreated CLL patients, and the incidence rises to 40-50% in fludarabine-refractory cases. It has been shown that TP53 mutations in the absence of del (17p) occur in a sizeable proportion of CLL patients (~5% in first line treatment situation) and are also associated with significantly worse outcome.

The European Research Initiative on CLL (ERIC) has a longstanding interest in the standardization and harmonization of diagnostic techniques for such aberrations including FISH ⌊to detect del (17p)⌋ and molecular (to detect TP53 mutations) analyses, providing guidelines to the international scientific community (Pospisilova et al, Leukemia 2012).

Until recently, no effective treatments were available for these patients, as chemo (immuno) therapeutic regimens could only achieve limited and short-lasting responses (e.g. PFS approx. 12 months with FCR in the 1st line setting) with a dismal prognosis despite additional lines of treatments, with the allogeneic transplant being the only potentially curative approach.

Recently, however, the outcome of CLL patients with del (17p) and/or TP53 gene mutation has improved dramatically by treatment with novel, non-chemotherapeutic agents such as the signaling inhibitors ibrutinib and idelalisib (the latter in combination with Rituximab) and the BCL-2 inhibitor venetoclax, which have been approved by the FDA and the EMA for this group of patients. That said, long term follow-up is required before drawing definitive conclusions regarding the extent to which TP53 gene disruption may maintain a prognostic role also with these novel agents.

Availability of these new drugs creates the need for practicing hematologists to carefully screen for del (17p) and TP53 gene mutations in all cases before the implementation of both first and subsequent lines of treatment in order to select the most appropriate treatment, while avoiding potentially ineffective regimens and unnecessary toxicity. This is especially timely given that the appropriate diagnostic techniques are currently not available or utilized in all centers treating CLL patients; furthermore, with few exceptions, quality control procedures are not in place.

AIMS+

OUR AIMS

ERIC aims to promote and/or advance the assessment of TP53 gene aberrations for diagnostic purposes by educating the hematological community about; 1) the need for performing such tests in all cases that require therapy, in both first and subsequent lines of treatment; 2) the quality of the appropriate techniques to be utilized by diagnostic laboratories to ensure reliable and comparable results across different institutions in Europe and elsewhere.

Ultimately, this will improve optimal patient care and will increase the availability of relevant tests, allowing clinical study groups, as well as the pharmaceutical industry, to focus on these particularly difficult-to-treat CLL patients and channel them to clinical trials aimed at further improving long-term outcomes.

The project is addressed to all scientific personnel working in laboratories performing diagnostics for patients with CLL including: those who have never performed the analyses in the past, those who have recently introduced novel diagnostics and need reassurance on the correctness of the procedure, and those already experienced in their use who need official certification of quality control for applied methodologies. It is also aims to increase physicians’ awareness of the need to test all CLL patients requiring therapy in order to select the most appropriate treatment for each case.

WORKING PLAN AND SPECIFIC OBJECTIVES
The project will accomplish its goals using the following approaches:

EDUCATIONAL EVENTS
1ST ERIC WORKSHOP ON TP53 ANALYSIS IN CLL
A hands-on workshop was held from 1-3 October, 2015 in Brno (Czech Republic) in which participants were introduced to both the scientific rationale for performing these diagnostic procedures and the basic principles of the relevant methodologies. This was the first ERIC TP53 Workshop on TP53 Analysis in Chronic Lymphocytic Leukemia. Its main goal was to address important biological, methodical and clinical questions relating to the role of TP53 abnormalities in Chronic Lymphocytic Leukemia. More than 130 participants from various countries were given the opportunity to learn, share ideas and discuss the current state of knowledge and future perspectives in a friendly atmosphere during the scientific sessions and social events. During the workshop, participants had a chance to explore the actual practical work, from the sample collection to the drafting of the final clinical report. This activity could also be extended to clinical study groups and industry partners to improve both the standardization of the assay and the interpretation of the results within investigator – or company-driven clinical trials.

2ND ERIC WORKSHOP ON TP53 ANALYSIS IN CLL
A hands-on workshop was held from 7-8 November, 2017 in Stresa (Italy). At this Workshop there was a special emphasis placed on both theoretical and practical aspects of p53 inactivation in leukemic cells, introduction of TP53 mutational analysis into the clinical diagnostics and data interpretation. There was also Panel discussions and an interactive workshop focusing on the practical aspects of TP53 analysis. The aim of the workshop was to attract top experts in the field to share their knowledge and experience. This event was organized by the Certifying Centre in Brno, Czech Republic who also organized the first TP53 Workshop.

ESTABLISHMENT AND EXPANSION OF THE TP53 NETWORK
A network of reference laboratories has been established and is providing ongoing supervision and advice to individual laboratories that need to set-up, improve or consolidate the diagnostic techniques for the assessment of TP53 gene aberrations in their laboratories. The current Network has grown and now consists of three Certifying Centers (Czech Republic, Germany and Sweden and Nordic Countries), for internal certification of the requesting labs, and eleven Reference Centers (originally eight), one for each participating country or region (Czech Republic, Denmark, France, Germany, Greece, Italy, Spain, Sweden and Nordic Countries, Switzerland, The Netherlands, United Kingdom), that will coordinate the work and ensure the overall quality of the network. The different centers will either help to set up the diagnostic procedures or directly perform the analyses for requesting laboratories while the latter are in the process of implementing them in their own facilities. ERIC is now a truly global network but aims to further expand this network in the future.

CERTIFICATION OF TP53 MUTATIONAL ANALYSIS
The certification process can be summarized as follows:

PHASE 1: COMPLETION OF PARTICIPATION FORM
Interested laboratories should complete the participation form in order to be eligible for the next certification round. The participation form can be found by clicking here

PHASE 2: LABORATORY AND BIOINFORMATICS ANALYSIS
Once the list of participating laboratories has been defined, these laboratories will be asked to confirm their shipping details and confirm that they still wish to participate.

The certifying centre will prepare the quality control material – genomic DNA from 5 CLL cases of diverse TP53 status – and ship this to the corresponding laboratories.

Laboratories will be informed as to when they should receive their samples and will be provided with instructions (via email) as to how to proceed with the certification process. The laboratories will be provided with the samples and all the necessary guidelines in order to carry out the analysis. The analysis will be completed through the submission of an online personalized form which must be sent within 3 months.

PHASE 3: EVALUATION & DECISION
The results will be analysed by the Certifying Centre in terms of both the analysis per se and the interpretation of the findings. Successful laboratories will be provided with a certificate (either Standard or Good Laboratory Practice) and a letter summarizing their performance and unsuccessful laboratories will be asked to reapply at the next round and be provided with necessary guidance.

SUMMARY: CERTIFICATION ROUNDS
Eight rounds of TP53 Certification have already been completed and the next round will be announced soon. The participation survey remains active for the whole year for those labs interested to participate in the next round. Should your lab be interested, then please ensure that you complete and send the Participation Form which can be found here

ONLINE WEB TOOLS
The following online web tools have been created and are available in order to provide laboratories with guidance and assistance to achieve reliable and comparable results for TP53 mutational analysis:

ONLINE HELP DESK
The online help desk has been specifically set up for laboratories facing any difficulties during the analysis. It provides methodological as well as interpretation consultation.

FREE SOFTWARE OF SANGER ANALYSIS DATA (GLASS)
This software helps laboratories with the analysis of Sanger Sequencing data.

GUIDANCE TOOLS FOR CERTIFICATION
TP53 CERTIFICATION REQUIREMENTS
A brief checklist summarizing what is needed to be successful in the certification round.

THE TP53 ANALYSIS TEMPLATE REPORT FORM
This template serves as an example in the correct and comprehensive result report that should be provided to the physicians.

A MANUAL FOR TP53 ANALYSIS
This manual contains concise information on the TP53 mutational analysis process from sampling to data interpretation.

STRUCTURE+
REFERENCE CENTRES
  • CZECHIA
  • DENMARK
  • FRANCE
  • GERMANY
  • GREECE
  • ITALY
  • SPAIN
  • SWEDEN AND NORDIC COUNTRIES
  • SWITZERLAND
  • THE NETHERLANDS
  • UNITED KINGDOM
CERTIFYING CENTER
  • CZECHIA
PARTICIPATION FORM+
TP53 NETWORK PARTICIPATION FORM
Full Name:
Institution: (Name that will appear on the diploma
Department:
Address to send the samples:
City:
Postal code:
Country:
E-mail:
Additional e-mail:
Phone:
Additional phone:
If your country doesn’t belong to the European Union, it is compulsory to provide the VAT/TAX number of your laboratory (HST, Federal Tax Number, ID…)
Tax number:
TP53 NETWORK PARTICIPATION FORM
Full Name:
Institution: (Name that will appear on the diploma
Department:
Address to send the samples:
City:
Postal code:
Country:
E-mail:
Additional e-mail:
Phone:
Additional phone:
If your country doesn’t belong to the European Union, it is compulsory to provide the VAT/TAX number of your laboratory (HST, Federal Tax Number, ID…)
Tax number:
HELP DESK+
TP53 NETWORK HELP DESK
Please remember to attach the sequence at the end of the form.
Sequences from both forward and reverse strand should be included.
Full Name:
Institution / Clinic:
City:
Postal code:
Country:
Case ID:
E-mail:
Phone:
Molecule type:
Method used:
If other method, please specify:
Enter your question:
I agree to have my case included in the ERIC database of problematic cases
Please upload your file(s) here (limit of 5 documents). Please attach the sequence in any of the supported formats.
Department:
Institution Address:
City:
Postal code:
Country:
E-mail:
Phone:
I agree to have my case included in the ERIC database of problematic cases
TP53 NETWORK HELP DESK
Please remember to attach the sequence at the end of the form.
Sequences from both forward and reverse strand should be included.
Full Name:
Institution / Clinic:
City:
Postal code:
Country:
Case ID:
E-mail:
Phone:
Molecule type:
Method used:
If other method, please specify:
Enter your question:
I agree to have my case included in the ERIC database of problematic cases
Please upload your file(s) here (limit of 5 documents). Please attach the sequence in any of the supported formats.(TXT, PDF, DOC)
Department:
Institution Address:
City:
Postal code:
Country:
E-mail:
Phone:
I agree to have my case included in the ERIC database of problematic cases
FAQ+

How long does the lab have to analyse the samples?
Normally two months. Deadlines will be outlined.

How long for results to be sent after submitting the results?
Deadline will be provided.

How should the results be submitted?
Via an online personalised form that you will be sent.

Who should I contact if I need assistance?
Please email the ERIC Office.

How long is the certification valid for?
Three years.

How can I renew my certification?
Renewals are made by GenQA and UK NEQAS LI. You can find all the information here.

How can I certify my lab?
Please complete the Participation Form

How long does it take to receive participation confirmation?
You will be contacted via email. This may take a few weeks.

Who decides whether my lab can participate?
The certifying centre in charge of the Round.

What happens if there are no more spaces available?
Your lab will be included in the next available Round.

Is Certification free?
Yes it is. All courier costs are covered by ERIC.

How many certification rounds are there per year and when will the next one be?
Normally 2 per year. Certification is open all year round. 4 rounds completed so far.

How long is the certification valid for?
Three years.

How can I renew my certification?
Renewals are made by GenQA and UK NEQAS LI. You can find all the information here.

How can I request a duplicate certificate?
Please contact the ERIC Office.

Which type of certification exists?
Standard and GLP (Good Laboratory Practice).

How many times can my lab reapply if unsuccessful?
There is no limit.

How can I find out more about certified labs?
Please click on the Certified centres and Certification Round sections on the website.

When will the samples be sent?
You will be informed via email.

How many samples will be sent?
You will receive five samples.

Which type of samples will be sent?
DNA samples.

Which techniques are being certified?
Next Generation Sequencing and Sanger Sequencing.

Can my lab certify for more than one technique?
Yes.

How long does the lab have to analyse the samples?
Normally two months. Deadlines will be outlined.

How long for results to be sent after submitting the results?
Deadline will be provided.

How should the results be submitted?
Via an online personalised form that you will be sent.

Who should I contact if I need assistance?
Please email the ERIC Office.

How long is the certification valid for?
Three years.

How can I renew my certification?
Renewals are made by GenQA and UK NEQAS LI. You can find all the information here.

How can I certify my lab?
Please complete the Participation Form

How long does it take to receive participation confirmation?
You will be contacted via email. This may take a few weeks.

Who decides whether my lab can participate?
The certifying centre in charge of the Round.

What happens if there are no more spaces available?
Your lab will be included in the next available Round.

Is Certification free?
Yes it is. All courier costs are covered by ERIC.

How many certification rounds are there per year and when will the next one be?
Normally 2 per year. Certification is open all year round. 4 rounds completed so far.

How long is the certification valid for?
Three years.

How can I renew my certification?
Renewals are made by GenQA and UK NEQAS LI. You can find all the information here.

How can I request a duplicate certificate?
Please contact the ERIC Office.

Which type of certification exists?
Standard and GLP (Good Laboratory Practice).

How many times can my lab reapply if unsuccessful?
There is no limit.

How can I find out more about certified labs?
Please click on the Certified centres and Certification Round sections on the website.

When will the samples be sent?
You will be informed via email.

How many samples will be sent?
You will receive five samples.

Which type of samples will be sent?
DNA samples.

Which techniques are being certified?
Next Generation Sequencing and Sanger Sequencing.

Can my lab certify for more than one technique?
Yes.