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.
| Original language | English |
|---|---|
| Pages (from-to) | 707-715 |
| Number of pages | 9 |
| Journal | Journal of Medical Genetics |
| Volume | 61 |
| Issue number | 7 |
| Early online date | 26 Mar 2024 |
| DOIs | |
| Publication status | Published - 20 Jun 2024 |
Bibliographical note
UKCGG dMMR consensus meeting attendees: Ruth Armstrong, Andrew Beggs, Cheryl Berlin, Adam Boyde, Angela Brady, Jeremy Bulmer, George Burghel, John Burn, Mark Catherwood, Joseph Christopher, Ruth Cleaver, Beth Coad, Hector Conti, Jacqueline Cook, Wei Cope, Gemma Corbett, Emma Crosbie, Rosemarie Davidson, Bianca DeSouza, Alan Donaldson, Miranda Durkie, Diana Eccles, Nicola Foot, Ian Frayling, Andrew George, Gareth Gerrard, Sarah Gibson, Andrew Green, Stephanie Greville-Heygate, Sarah Hamilton, Helen Hanson, Rachel Hart, Shirley Hodgson, Debbie Holliday, Jacqui Hoyle, Rosalyn Jewell, Zoe Kemp, Louise Kiely, Vicki Kiesel, Kelly Kohut, Rebecca Kristeleit, Ajith Kumar, Fiona Lalloo, Andrew Latchford, Natalie Lee, Donna Lobo, Maurice Loughrey, Suzanne MacMahon, Richard Martin, Sally Martin, Terri McVeigh, Zosia Miedzybrodzka, Eleanor Minshall, Kevin Monahan, Laura Monje-Garcia, Meleri Morgan, Hood Mugalaasi, Jennie Murray, Hannah Musgrave, Emily Nastali, Gail Norbury, Kai Ren Ong, Nicola Onyeador, Judith Pagan, Kezia Quigley, Elizabeth Ratsma, Gillian Rea, Dimitra Repana, Adam Rosenthal, Malcolm Scott, Claire Searle, Adam Shaw, Lucy Side, Kate Simon, Katherine Smith, Joyce Solomons, Avani Varde, Nick West, Jennifer Wiggins, Dorte Wren, Laura Yarram-Smith.Keywords
- Humans
- United Kingdom/epidemiology
- DNA Mismatch Repair/genetics
- Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
- Consensus
- Colorectal Neoplasms/genetics
- Microsatellite Instability
- Genetic Testing
- Neoplastic Syndromes, Hereditary/genetics
- Genetic Predisposition to Disease
- Brain Neoplasms
