Extent of investigation and management of cases of 'unexplained' mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus.
Loading...
Embargo End Date
ICR Authors
Authors
McVeigh, TP
Monahan, KJ
Christopher, J
West, N
Scott, M
Murray, J
Hanson, H
UKCGG dMMR Consensus Meeting Attendees
Monahan, KJ
Christopher, J
West, N
Scott, M
Murray, J
Hanson, H
UKCGG dMMR Consensus Meeting Attendees
Document Type
Journal Article
Date
2024-06-20
Date Accepted
2024-03-09
Abstract
BACKGROUND: Mismatch repair deficiency (dMMR) is a characteristic feature of cancers linked to Lynch syndrome. However, in most cases, it results from sporadic somatic events rather than hereditary factors. The term 'Lynch-like syndrome' (LLS) has been used to guide colorectal cancer surveillance for relatives of individuals with a dMMR tumour when somatic and germline genomic testing is uninformative. As the assessment of mismatch repair through immunohistochemistry and/or microsatellite instability is increasingly applied across various tumour types for treatment planning, dMMR is increasingly detected in tumours where suspicion of hereditary aetiology is low. Our objective was to establish current practices and develop national guidance for investigating, and managing relatives of, patients with cancers demonstrating unexplained dMMR. METHODS: This was achieved through a virtual consensus meeting involving key stakeholders from the UK, through premeeting surveys, structured discussions and in-meeting polling to formulate best practice guidance. RESULTS: We identified variability in the availability of diagnostic technologies across specialist centres. It was agreed that equitable access to baseline testing is required, acknowledging the need for a pragmatic approach to investigating dMMR cancers not traditionally associated with Lynch syndrome. Factors such as family history, age, tumour type, protein loss pattern and extent of the investigation were deemed crucial in guiding family management. The term 'unexplained dMMR' was recommended over LLS. CONCLUSION: Decisions regarding investigations and future cancer risk management in patients and relatives should be nuanced, considering factors like clinical suspicion of hereditary predisposition to allocate limited resources efficiently and avoid unnecessary investigations in low-suspicion families.
Citation
Journal of Medical Genetics, 2024, 61 (7), pp. 707 - 715
Source Title
Journal of Medical Genetics
Publisher
BMJ PUBLISHING GROUP
ISSN
0022-2593
eISSN
1468-6244
1468-6244
1468-6244
Collections
Research Team
Cancer Genetics Edu&Qual