Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996-2020: development of a national resource of patient-level genomics laboratory records.
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Date
2022-12-26ICR Author
Author
Loong, L
Huntley, C
McRonald, F
Santaniello, F
Pethick, J
Torr, B
Allen, S
Tulloch, O
Goel, S
Shand, B
Rahman, T
Luchtenborg, M
Garrett, A
Barber, R
Bedenham, T
Bourn, D
Bradshaw, K
Brooks, C
Bruty, J
Burghel, GJ
Butler, S
Buxton, C
Callaway, A
Callaway, J
Drummond, J
Durkie, M
Field, J
Jenkins, L
McVeigh, TP
Mountford, R
Nyanhete, R
Petrides, E
Robinson, R
Scott, T
Stinton, V
Tellez, J
Wallace, AJ
Yarram-Smith, L
Sahan, K
Hallowell, N
Eccles, DM
Pharoah, P
Tischkowitz, M
Antoniou, AC
Evans, DG
Lalloo, F
Norbury, G
Morris, E
Burn, J
Hardy, S
Turnbull, C
Type
Journal Article
Metadata
Show full item recordAbstract
OBJECTIVE: To describe national patterns of National Health Service (NHS) analysis of mismatch repair (MMR) genes in England using individual-level data submitted to the National Disease Registration Service (NDRS) by the NHS regional molecular genetics laboratories. DESIGN: Laboratories submitted individual-level patient data to NDRS against a prescribed data model, including (1) patient identifiers, (2) test episode data, (3) per-gene results and (4) detected sequence variants. Individualised per-laboratory algorithms were designed and applied in NDRS to extract and map the data to the common data model. Laboratory-level MMR activity audit data from the Clinical Molecular Genetics Society/Association of Clinical Genomic Science were used to assess early years' missing data. RESULTS: Individual-level data from patients undergoing NHS MMR germline genetic testing were submitted from all 13 English laboratories performing MMR analyses, comprising in total 16 722 patients (9649 full-gene, 7073 targeted), with the earliest submission from 2000. The NDRS dataset is estimated to comprise >60% of NHS MMR analyses performed since inception of NHS MMR analysis, with complete national data for full-gene analyses for 2016 onwards. Out of 9649 full-gene tests, 2724 had an abnormal result, approximately 70% of which were (likely) pathogenic. Data linkage to the National Cancer Registry demonstrated colorectal cancer was the most frequent cancer type in which full-gene analysis was performed. CONCLUSION: The NDRS MMR dataset is a unique national pan-laboratory amalgamation of individual-level clinical and genomic patient data with pseudonymised identifiers enabling linkage to other national datasets. This growing resource will enable longitudinal research and can form the basis of a live national genomic disease registry.
Collections
Subject
Databases, Genetic
Genetic Testing
Genetics, Medical
Genetics, Population
Genomics
Research team
Translational Genetics
Cancer Genetics Edu&Qual
Language
eng
Date accepted
2022-11-18
License start date
2022-12-26
Citation
Journal of Medical Genetics, 2022, pp. jmg-2022-108800 -
Publisher
BMJ PUBLISHING GROUP