Journal Article

Extent of investigation and management of cases of ‘unexplained’ mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus

Scott, Malcolm, Mugalaasi, Hood, Morgan, Meleri, Cook, Jacqueline, Rosenthal, Adam, Greville-Heygate, Stephanie, Berlin, Cheryl, Ong, Kai Ren, Crosbie, Emma, Smith, Katherine, McVeigh, Terri Patricia, Onyeador, Nicola, Bulmer, Jeremy, Donaldson, Alan, McVeigh, Terri, Searle, Claire, Hamilton, Sarah, Cleaver, Ruth, Foot, Nicola, Martin, Richard, Norbury, Gail, Beggs, Andrew, Loughrey, Maurice, Christopher, Joseph, Lalloo, Fiona, Side, Lucy, Shaw, Adam, Burn, John, Hodgson, Shirley, Solomons, Joyce, MacMahon, Suzanne, Musgrave, Hannah, Ratsma, Elizabeth, Minshall, Eleanor, Kiesel, Vicki, Kristeleit, Rebecca, Kemp, Zoe, Gerrard, Gareth, Kiely, Louise, Lee, Natalie, Kohut, Kelly, Varde, Avani, Miedzybrodzka, Zosia, George, Andrew, Hoyle, Jacqui, Latchford, Andrew, Lobo, Donna, Yarram-Smith, Laura, Repana, Dimitra, Simon, Kate, Holliday, Debbie, Martin, Sally, Corbett, Gemma, DeSouza, Bianca, Wren, Dorte, Jewell, Rosalyn, Murray, Jennie, Kumar, Ajith, Eccles, Diana, Gibson, Sarah, Green, Andrew, Pagan, Judith, Davidson, Rosemarie, Wiggins, Jennifer, Frayling, Ian, Brady, Angela, Coad, Beth, Durkie, Miranda, Hart, Rachel, Mona

2024

نظرة عامة

BackgroundMismatch 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.MethodsThis 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.ResultsWe 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.ConclusionDecisions 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.

• الناشر: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• موضوع: Brain Neoplasms / Cancer / Cancer Genetics / Clinical Decision-Making / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - diagnosis / Colorectal Neoplasms - genetics / Colorectal Neoplasms - therapy / Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis / Colorectal Neoplasms, Hereditary Nonpolyposis - genetics / Colorectal Neoplasms, Hereditary Nonpolyposis - therapy / Consensus / Disease management / DNA Mismatch Repair - genetics / Endometrial cancer / Etiology / Family medical history / Genetic disorders / Genetic Predisposition to Disease / Genetic Testing / Genetics / Humans / Immunohistochemistry / Medical research / Medical screening / Microsatellite Instability / Mismatch repair / Neoplastic Syndromes, Hereditary - diagnosis / Neoplastic Syndromes, Hereditary - genetics / Neoplastic Syndromes, Hereditary - therapy / Patients / Tumors / United Kingdom - epidemiology / Yeast