Genetics Quality and Accreditation workshop Manchester ... · PDF fileGenetics Quality and...

CEQAS is a member of the consortium

Genetics Quality and Accreditation workshop

Manchester 17th May 2017

Katrina Rack

Oxford


____________________________________________________________________________________________________________ CEQAS

What is CEQAS

Types of schemes

Scheme update

Highlights 2016

Key recommendations


____________________________________________________________________________________________________________

CEQAS Background

External Quality Assessment scheme

assesses laboratories analytical and interpretive

performance compared to other laboratories by testing the

accuracy and quality of the results

Part of the UK NEQAS Consortium

Not for profit organisation

Accredited EQAs (ISO17043)


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CEQAS : what we do

Largest European Cytogenetic Scheme

Widest repertoire of cytogenomic EQAs

35 EQAs – cytogenetics, molecular cytogenetics, PGD,

NIPT, acquired disorders, clinical genetics


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EQAs 2017

Acquired

Acute lymphoblastic Leukaemia

CNS tumours - 1p/19q co-deletion, MGMT, IDH

Myeloid Disorders

Mature B&T Cell Neoplasms(2)

Microarray for acquired disorder

Myeloma

Sarcoma (FFPE FISH & RT-PCR)

Neuroblastoma pilot

Renal Carcinoma pilot

Lymphoma pilot (FFPE FISH)

Preimplantation Genetic diagnosis

PGD array/NGS (blastomere/trophectoderm/PB)

aneuploidy and rearrangement (3)

PGD FISH (blastomere)

PGD Sperm FISH

Constitutional

Amniotic fluid

Blood

Chorionic villus

FISH rapid aneuploidy

Molecular rapid aneuploidy

Products of conception(2)

Prenatal Microarray

Postnatal Microarray

Pilot NIPT

Pilot Breakage

Genetic Counselling

Cardiovascular genetics

Monogenetic disorder

Dysmorphology

Oncogenetics


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CEQAS : EQA organisation

Submission in 5 European Languages

Submissions assessed against

European Cytogenetic and reporting Guidelines

ISCN 2016

ISO15189

CEQAS offers EQAs to laboratories worldwide


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CEQAS : Participants

Genetic laboratories

Molecular pathology laboratories

Haematology laboratories

Prenatal diagnostic testing laboratories and

companies

Clinical genetic centres


Participating labs 2016

51 countries

34 European countries

6 continents


____________________________________________________________________________________________________________ Enrolled Laboratories & EQAs

0

200

400

600

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1000

1200

1400

1600

1800

2010 2011 2012 2013 2014 2015 2016

To

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Total EQA Enrolments 2010 - 20160

50

100

150

200

250

300

350

400

2010 2011 2012 2013 2014 2015 2016

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Enrolled laboratories 2010 - 2016


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EQA Types of tests offered

Historically EQAs provided for cytogenetic analysis and FISH.

As new technologies introduced in the laboratories EQAs evolved

to incorporate these: Arrays, NGS

As complementary tests introduced or required as part of the

diagnostic or work up procedure EQAs evolved to include mutation

screening and epigenetic changes

Traditional cytogenetic/molecular genetic boundaries are

disappearing in the laboratories – requires EQA providers to

respond to this.

CEQAS runs joint EQAs with both UK NEQAS for molecular

genetics and EMQN.

Will mean closer collaboration needed in the future


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EQA Techniques assessed

Karyotyping

FISH

QF-PCR

MLPA

Arrays

NGS copy number analysis

Gene mutation analysis and epigenetic changes (1)

RT-PCR for cancer fusion genes


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EQA Types of EQA

Sample

Distribution of samples for analysis (DNA, amplified

DNA, fixed cells, FFPE slides)

Online

Analysis of G-band and FISH images online

Serial EQA for Clinical Genetics

Educational case scenarios for clinical genetics


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CEQAS : How are EQAs run

Each EQA assessedby a group of assessors

Experienced clinical scientists, clinicians or pathologists

with necessary competency in relevant genetic testing field

85 Assessors from 15 countries

Agreed Marking Criteria and Performance Criteria

Two performance designations:

Satisfactory

Poor


Prenatal

Constitutional

SAG

Amniotic fluid

CVS

Prenatal

Microarray

Products of

conception (G)

Products of

conception

(Arr/MLPA/PCR)

Scientific Advisory Board (SAB)

PGD SAG

PGD

array/NGS

aneuploidy

rearrangement

PGD FISH

(blastomere)

PGD Sperm

FISH

Rapid

Prenatal

SAG

FISH rapid

aneuploidy

Molecular

rapid

aneuploidy

(QF-PCR/

MLPA/BoBs)

Pilot NIPT

Postnatal

Constitutional

SAG

Blood

Microarray

(postnatal)

Breakage

Genetic

Counselling

SAG

Cardiovascular

genetics

Monogenetic

disorder

Dysmorphology

Oncogenetics

Haematology

SAG

ALL

Myeloid

Mature B&T

x2 (G or FISH)

Microarray

for acquired

disorders

Myeloma

Lymphoma

pilot (FFPE

FISH)

Oncology

SAG

CNS

Sarcoma

Neuro-

blastoma

Renal

Carcinoma

Joint SAGs with UK

NEQAS molecular biology


____________________________________________________________________________________________________________

New EQAs : On going development

Genetic counselling

Educational EQA

Aimed at Clinical Geneticists

Developed at the request of ESHG

Will expand to include genetic counsellors


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Consists of an unfolding case scenario

Sequential EQA – stepwise access to case details

dependant on completion of each stage

Each stage requires counsellor to outline what

questions to ask, what to discuss and what tests to

request

Stage 1: 1st consultation

Referral letter, examination, family history, genetic

testing requests based on differential diagnosis

Stage 2/3: 2nd/3rd consultations.

Feedback of initial results. Request further patient or

family testing as required. Advice to patients and other

family members


____________________________________________________________________________________________________________

Case scenarios based on real life consultations

Specialities covered

Dysmorphology

Cardiology

Cancer genetics

Monogenic disorders

Future: Provision of EQA for Genetic

counsellors


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Scheme update 2016

New EQAs

Neuroblastoma (Array, FISH)

Renal cell carcinomas (retrospective)-

development to include mutation

screening

NIPT

Breakage syndromes

Lymphoma


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Aims of EQA

Highlight areas of concern where laboratories are struggling

What essential tests to perform

Best technique to use

How to interpret results – particularly atypical results

What to include in a report – clarity, is it clear and concise

EQA providers can facilitate this

Provide experience of EQA outcome

Capability of bringing together the experience of large number of

laboratories

Independent

Results in Best practice meetings and establishment of guidelines

and recommendations.


____________________________________________________________________________________________________________

Best Practice meetings: Sperm FISH 04/04/2017

Feedback from EQA

What parameters to report

Cut offs to apply to distinguish normal and

abnormal results

No specific guidelines

Now in preparation


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Best Practice meetings: Prenatal array 20/04/2017

No European guidelines, some national guidelines

Feedback from EQA

Different reporting strategies of CNVs

Unsure how to report absence of heterogeneity (AOH)

Survey on interpretation of pathogenicity of CNVs.

Good consensus for pathogenic and benign CNVs.

Variation classification intermediate groups

Another survey planned

Findings will be presented at ACGS meeting


____________________________________________________________________________________________________________

Best Practice meetings: CNS tumours 10/05/2017

Feedback from EQA

Difficulties in reporting atypical FISH patterns: report

or not? is it important?

Methylation studies- variable number of sites

Variable cut offs, how to establish internal validation


New WHO classification system to integrate


____________________________________________________________________________________________________________

Best Practice meetings: PGD December 2017

Feedback from array/NGS Polarbody

blastomere/trophectoderm aneuploidy/rearrangement EQAs

How to describe results in the context of a haploid

genotype (Polar Body)

Interpretation of results – relationship of abnormal results

to chromosome abnormalities and therefore correct advice



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Best Practice Guidelines

Guidelines in preparation

Update Haematology

Update Constitutional

Sperm FISH

Oligodendroglioma (CNS)

Array/NGS PDG

NIPT – guidelines genetic testing, in press

To start

Lymphoma


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Whats happening 2017

Survey labs aim development new EQAs or reorganisation of

existent EQAs

Working more closely with UK NEQAS for Molecular Genetics

to develop further EQAs.

Joint PGD SAG and Joint Rapid prenatal SAG. New Joint

Oncology SAG.

Will facilitate better provision of EQAs to participants.


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Key recommendations

How to be successful at EQA

Don’t deviate from normal procedure

Don’t over interpret results

Keep reports concise

Put all essential test results in a prominent position in report,

ideally in a summary box

Take on board any comments – learn from others

Recognise that errors can occur in any laboratories despite

rigorous procedure

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