Extent of investigation and management of cases of 'unexplained' mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus.
Date
2024-06-20ICR Author
Author
McVeigh, TP
Monahan, KJ
Christopher, J
West, N
Scott, M
Murray, J
Hanson, H
UKCGG dMMR Consensus Meeting Attendees
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Clinical Decision-Making
Humans
United Kingdom
DNA Mismatch Repair
Colorectal Neoplasms, Hereditary Nonpolyposis
Consensus
Colorectal Neoplasms
Microsatellite Instability
Genetic Testing
Neoplastic Syndromes, Hereditary
Genetic Predisposition to Disease
Brain Neoplasms
Research team
Cancer Genetics Edu&Qual
Language
eng
Date accepted
2024-03-09
License start date
2024-06-20
Citation
Journal of Medical Genetics, 2024, 61 (7), pp. 707 - 715
Publisher
BMJ PUBLISHING GROUP