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Molecular Pathology & Biobanking Core facility

In recent years, the need for controlling the 'secondary use' of human biospecimens for research purposes at the NKI became more apparent. To ensure human material is used properly and efficiently, especially in the case of scarce, valuable samples, a facility for use of NKI biobank materials was desired. Therefore, in 2011, the Core Facility Molecular Pathology & Biobanking (CFMPB) was founded.

The CFMPB facilitates the use of NKI biobank materials for translational research. For all research projects, in which the use of NKI biobank materials is proposed, the Core Facility has to be contacted by the researcher. The CFMPB confirms that the Translational Research Board approves the usage of the material, does the sample handling (logistics), generates derivative biospecimen samples, and stores scientific results. Currently the facility's resources consist of a team of dedicated (lab) staff, dedicated lab space and equipment, and an in-house developed application and request tool.

Application and Request Tool

In collaboration with the IT department we are developing a web application named the Application and Request Tool (ART) in a lean and agile way. ART serves many users; Researchers can access ART for online application of studies and biospecimen-and lab-work order requests. Pathologist, clinicians and basic scientists use the system for reviewing and approving the study applications. The CFMPB staff uses ART as a workflow system, handling the applications and requests. All this user activity is stored in the ART database and by doing so, information about the applications, biospecimen identifiers, succeeding actions and derivatives accumulates. This results in a rich data source allowing the CFMPB to further optimize and stimulate proper use of NKI-AVL biobank specimens. 'ART' includes a (connector based) search tool option to query existing hospital data systems as PALGA, LMS, Biometrics tumor registry, GLIMMS, etc.

ART is developed in .Net (C# and asp.net), stores the data in a Microsoft SQL Server database, is supported and hosted by the IT department and is only accessible on the intranet (http://cf-mpb.nki.nl).

Study Application and Approval

The CFMPB follows a standard procedure for all requests of human biospecimens for (translational) research. The NKI Translational Research Board (TRB) has decided that each study using NKI Biobank material (secondary use of diagnostic material) needs to be reviewed by three internal NKI reviewers.

1. a relevant pathologist (tissue) or clinical chemist (serum/blood)
2. a relevant clinician
3. a relevant basic scientist

The CFMPB, on behalf of the TRB, will verify the suitability of the reviewers for the particular application. The TRB approval procedure for 'secondary use' of human material (according to Dutch legislation (Code of conduct)) is, following positive recommendation of the Medical Ethical Committee (NKI), approved by the Board of Directors NKI.

Only NKI employees can submit applications. External applicants need to initiate a collaboration with an NKI employee. The NKI-AVL partner will be responsible for the use of the material and should be involved in the research and publications. In many cases, a Material Transfer Agreement (MTA) from the Technology Transfer Office is required (see website of the NKI TTO).

NKI Biobanks regulations and Legislation

The NKI has several Biobank collections and these biospecimens can only be requested for research purposes through the CFMPB. Most of these samples are collected during diagnostic procedures or treatment and are stored primarily for patient care. They can be used for research purpose, 'secondary use', according to the Dutch legislation: Code of Conduct (FEDERA) and WGBO (Wet op de geneeskundige behandelingsovereenkomst). The Code of conduct is the Dutch standard for collection, storage and use of human materials for scientific research.  http://www.federa.org/gedragscodes-codes-conduct-en

Part of the material is specifically collected for (predefined) scientific research and stored primarily for research. In these cases there is always explicit informed consent.  Use of this material is regulated by WMO (wet medisch wetenschappelijk onderzoek met mensen/law for medical scientific research with interventions in humans), WGBO and Code of Conduct Federa.  These 'de novo' studies always need approval by the Medical Ethical Committee (MEC)

Biobank Collections

Department of Pathology (secondary use and de novo)
1. Biobanks of tissue collected during the diagnostic and treatment process of patients
2. Paraffin tissue archive (> 1970)
3. Glass slides archive (> 1970)
4. Frozen tissue biobank (> 1985)

Department Clinical Chemistry (de novo and secondary use)

1. 1.Serum collection (>1982)
2. Blood biobank (>2010)

CFMPB (secondary use)

1. DNA
2. RNA
3. Protein
4. Digital slides
5. IHC data & results

Lab facilities

The CFMPB has a fully equipped and dedicated histology/immunohistochemistry (IHC) lab.  Nearly all IHC is performed using the BenchMark Ultra (Ventana, Roche) automated stainer, in close collaboration with the diagnostic pathology department. 
All routine IHC diagnostic protocols are also implemented at the CFMPB and can be requested for research studies.  Ample experience is available for the development of new antibody staining protocols.  Elaboration and optimizing of staining protocols is performed in close collaboration with the requesting scientist and involved pathologist. 
 
We are in the process of implementing digital pathology for scoring and storage of all research IHC using Aperio ScanScope (Leica), Spectrum and Slidepath software tools in combination with ART.

To guarantee standard quality all DNA and RNA isolations from NKI Biobank material (FFPE, FF, serum, and blood) are performed by, or under supervision of, the CFMPB technicians. All samples will be handled and stored in the dedicated CF lab (pre-PCR, QC conditions) under supervision of the coordinating technicians according to standard protocols modified and adapted to the specific requirements per project. Small (pilot) studies (less then ~10 samples) will be carried out by the CFMPB technicians. All larger studies require technical support from the applicant.

We register all used samples and results obtained (IHC, DNA/ RNA quality and quantity). All resulting samples will be coded with a unique (bar-coded) core-study number before distribution for further use. The decoding key will be kept in a secured database of the pathology department (and will be, depending on the study design and consent, always accessible for the applicant). 

The central contact of the CFMPB is CFMP@nki.nl or +31 20 512 9146.
We are located at the department of Molecular Pathology.

Projects

We are collaborating in the following projects:

  • FP7-HEALTH-2010-2.4.1-2 EUROCAN " A European Platform for Translational Cancer Research " contribution in WP10 Biobanking/WP11 Clinial Epidemiology C
  • CTMM TraIT "Translational IT".  Involved in WP3 Biobanking, WP7 digital pathology and WP5 FP7
  • HEALTH-2007-2.4.1-11 COGS "Collaborative Oncological Gene-environment Study" -BCAC (with MK Schmidt) P7 HEALTH-2009-2.1.1-2
  • BASIS  "Breast Cancer Somatic Genetics Study" (Subcontractor with Laura Van't Veer)

Publications

  • An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer.
    Majewski IJ, Kluijt I, Cats A, Scerri TS, de Jong D, Kluin RJ, Hansford S, Hogervorst FB, Bosma AJ, Hofland I, Winter M, Huntsman D, Jonkers J, Bahlo M, Bernards R.
    J Pathol. 2012 Dec 3. doi: 10.1002/path.4152.
  • Indentification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. 
    Majewski IJ, Mittempergher L, Davidson NM, Bosma A, Willems SM, Horlings HM, de Rink I, Greger L, Hooijer GK, Peters D, Nederlof PM, Hofland I, de Jong J, Wesseling J, Kluin RJ, Brugman W, Kerkhoven R, Nieboer F, Roepman P, Broeks A, Muley TR, Jassem J, Niklinski J, van Zandwijk N, Brazma A, Oshlack A, van den Heuvel M, Bernards R. 
    J Pathol. 2013 Jul;230(3):270-6. doi: 10.1002/path.4209.

Employees

Broeks, Annegien.jpg

Experience

Following my MSc. at the Free University and PhD in 1997 in the group of Ronald Plasterk, I became a postdoc/Associate-Staff-Scientist in the group of Laura Van't Veer at the NKI. I have worked on several Dutch Cancer Society projects studying e.g. cancer susceptibility genes and radiation-induced breast cancer.  In 2010 I accepted a new challenge: the development of the CFMPB. I coordinate all processes supported by the facility.  An important aspect is guarding the process according to the Dutch regulation and legislation: 'WMO' and 'code of conduct'. In addition I continued doing research in close collaboration with Marjanka Schmidt.

 

 

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Jose Overwater

Office Manager CF-MPB

Personal details

Experience

I started working as Office manager at the NKI in 1991 at the department of Carcinogenesis. After working on several other departments, I started in 2011 at the new CFMPB.
The main tasks are tracking and processing of all new applications and (lab) work orders using 'ART'. I manage the cfmp@nki.nl email inbox for all the project correspondence. Furthermore, I support external tissue requests and register all materials in PALGA and LMS.

 

 

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Linde Braaf, BSc

Coordinating technician molecular genetics - Lab Manager CF-MPB

Experience

In 2004 I got my bachelor degree in life sciences and started working at the NKI in the group of  Laura Van 't Veer, with Annegien Broeks, as a technician. I am, and have been,  involved in several molecular genetic breast cancer projects. In 2010 I joined the CFMPB as a Coordinating technician of the molecular genetics studies. In 2011 I also started as a lab manager of the division of Molecular Pathology where I am involved in the organization of this division.

 

 

 

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Broersen, Sanne

Sanne Broersen

Technician

Personal details

Experience

After finishing my bachelor's degree at InHolland I started working as technician in the CFMPB group of Annegien Broeks. At the core facility I am mainly working on DNA/RNA isolations, immunohistochemistry staining and preparing TMA's. With this I support different CFMPB-studies.

 

 

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Ingrid Hofland

Coordinating technician

Personal details

Experience

I perform and coordinate all immunohistochemistry (IHC) experiments in the CF-MPB. Nearly all IHC is performed using the BenchMark Ultra (Ventana, Roche) automated stainer, in close collaboration with the diagnostic pathology department.  All routine IHC diagnostic protocols are also implemented in the CF-MPB and can be requested for research studies. I have ample experience with development of new antibody staining protocols. Elaboration and optimizing of staining protocols is performed in close collaboration with requesting scientists and involved pathologists.  Protocols are developed, if possible, for automated staining with the BenchMark Ultra.

 

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Holman, Esther

Esther Holman

Medisch administratief medewerker

Personal details

Experience

My name is Esther Holman I started to work at the NKI at 1990. I have worked in the glassware facility for 23 years' but since last year April I started to work at the CFMPB. My main tasks are assisting Jose Overwater with all kind of study and administration activities.

 

 

 

 

 

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Donne Majoor

Tecnician

Personal details

Experience

I work already for 23 years as a technician in the department of Diagnostic Pathology at the AVL. In 2011 I started to work at the CFMPB for two days a week. I am specialized in histology skills and experienced in developing new research IHC protocols.

 

 

 

 

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Dennis Peters

Technician

Personal details

Experience

I started working at the NKI in May 2012 directly after I obtained my bachelor in science degree (Life Sciences & Chemistry Hoge school Utrecht). My job is to support different studies within the CFMPB for molecular genetics and immunohistochemistry. I perform a number of techniques as DNA/RNA/protein isolations, (q-) PCR's, SNaPshot mutation analysis, as well as immunohistochemistry staining using the BenchMark Ultra (Ventana, Roche) automated stainer.

 

 

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Sanders, Pathologie Antoni van Leeuwenhoek (AVL).

Joyce Sanders

Research pathologist

Personal details

Experience

Joyce is working at the NKI as research pathologist.

 

 

 

 

 

 

 

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Vonk Kuijl Astrid

Astrid Vonk

Office manager

Experience

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