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UK recommendations for SDHA germline genetic testing and screening in clinical practice

UK recommendations for SDHA germline genetic testing and screening in clinical practice
UK recommendations for SDHA germline genetic testing and screening in clinical practice
SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.
0022-2593
Hanson, Helen
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Durkie, Miranda
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Lalloo, Fiona
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Eccles, Diana
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Maher, Eamonn R.
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Izatt, Louise
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McVeigh, Terri P.
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Cook, Jackie A.
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Brewer, Carole
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Drummond, James
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Butler, Samantha
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Cranston, Treena
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Casey, Ruth
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Tan, Tricia
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Morganstein, Daniel
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Tischkowitz, Marc
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Turnbull, Clare
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Woodward, Emma Roisin
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UK Cancer Genetics Centres
Hanson, Helen
fe4a8065-8b0d-4b30-a658-cd433570c2ec
Durkie, Miranda
7caca497-e12f-4f13-99e0-f40e767f0163
Lalloo, Fiona
d7ac29ee-10db-49a5-af3c-265b6d1c113d
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Maher, Eamonn R.
577b8856-f8a8-49c2-9484-288d9f964aed
Izatt, Louise
5d6201a8-8a56-4923-ac9d-75dca6be0a40
McVeigh, Terri P.
315c9c27-9756-4740-bced-b06bc774163c
Cook, Jackie A.
f7dc302c-13c7-4a29-9056-484084693dd3
Brewer, Carole
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Drummond, James
cd3377cb-42d4-43e8-a230-cf37967aa94b
Butler, Samantha
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Cranston, Treena
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Casey, Ruth
ee3d6b85-ed9f-4f69-9cc0-09179a849acf
Tan, Tricia
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Morganstein, Daniel
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Tischkowitz, Marc
dde7a0ce-14a3-4171-8f9c-c3f4d0623735
Turnbull, Clare
11b8255e-4fee-407e-807e-59da6d67d8bc
Woodward, Emma Roisin
3227793f-40d7-4d27-9fae-4cba203d44a3

Hanson, Helen, Durkie, Miranda, Lalloo, Fiona, Izatt, Louise, McVeigh, Terri P., Cook, Jackie A., Brewer, Carole, Drummond, James, Butler, Samantha, Cranston, Treena, Casey, Ruth, Tan, Tricia, Morganstein, Daniel, Tischkowitz, Marc, Turnbull, Clare and Woodward, Emma Roisin , UK Cancer Genetics Centres (2022) UK recommendations for SDHA germline genetic testing and screening in clinical practice. Journal of Medical Genetics. (doi:10.1136/jmedgenet-2021-108355).

Record type: Article

Abstract

SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.

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More information

Accepted/In Press date: 13 February 2021
e-pub ahead of print date: 8 March 2022
Additional Information: Funding HH and FL are supported by Cancer Research CRUK Catalyst Award, CanGene-CanVar (C61296/A27223). RC is supported by GIST Support UK. ERW is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). EM thanks the NIHR Cambridge Biomedical Research Centre for support. The University of Cambridge has received salary support (EM) from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health.

Identifiers

Local EPrints ID: 455107
URI: http://eprints.soton.ac.uk/id/eprint/455107
ISSN: 0022-2593
PURE UUID: 99b060d6-ed46-4494-b811-9692be9f2450
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 09 Mar 2022 17:44
Last modified: 10 Mar 2022 02:32

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Contributors

Author: Helen Hanson
Author: Miranda Durkie
Author: Fiona Lalloo
Author: Diana Eccles ORCID iD
Author: Eamonn R. Maher
Author: Louise Izatt
Author: Terri P. McVeigh
Author: Jackie A. Cook
Author: Carole Brewer
Author: James Drummond
Author: Samantha Butler
Author: Treena Cranston
Author: Ruth Casey
Author: Tricia Tan
Author: Daniel Morganstein
Author: Marc Tischkowitz
Author: Clare Turnbull
Author: Emma Roisin Woodward
Corporate Author: UK Cancer Genetics Centres

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