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

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

<jats:sec><jats:title>Objective</jats:title><jats:p>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 Ser...

وصف كامل

التفاصيل البيبلوغرافية
المؤلفون الرئيسيون: 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, Burn, J, Morris, E, Hardy, S
التنسيق: Journal article
اللغة:English
منشور في: BMJ Publishing Group 2022
الوصف
الملخص:<jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>

مواد مشابهة