The Value Of Germline Mutation Testing In Serrated Polyposis Syndrome

IntroductionSerrated Polyposis Syndrome (SPS) is now known to be the commonest polyposis syndrome. Previous analyses for germline mutations have shown no consistent positive findings1. To exclude other polyposis syndromes, new 2019 BSG guidelines2 advise gene panel testing if: the patient is under 50 years of age; if there are multiple affected individuals within a family; or if there is dysplasia within any of the polyps.MethodsA database of patients with SPS according to the WHO 2019 criteria3 was established at the Oxford University Hospitals NHS Trust. Data collection began in 2010 and in total there are 192 SPS patients. The results of any patients sent for genetic testing were analysed.ResultsOut of 192 patients, 76 underwent genetic testing. The majority were tested for a hereditary colorectal cancer panel including MUTYH, APC, PTEN, SMAD4, BMPR1A, STK11 and Lynch syndrome mismatch repair genes. Of these, 14 had a positive genetic test result. Table 1 characterises patient with positive results.Conclusions7% (14/192) of SPS patients were affected by heterozygous germline mutations, higher than in previous series1, including previously unreported associations with CHEK2 and POLD1. This led to a change in management for patients or their families in seven cases. Only 57% (8/14) of these patients would have been recommended for gene panel testing in the current BSG guidelines2. Detection of germline mutations could have significant impact on risk assessment and clinical management, including advice on extra-colonic surveillance in patients and their family members.ReferencesClendenning M, Young JP, Walsh MD, et al. Germline mutations in the polyposis-associated genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 are not common in individuals with serrated polyposis syndrome. PLoS ONE 2013;8:e66705. Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411–444. Rosty C, Brosens LAA, Nagtegaal ID. Serrated Polyposis. WHO Classification of Tumours. Digestive System Tumours, 2019.