Low Yield of Genetic Testing in Serrated Polyposis Syndrome

Area of Science:

• Gastroenterology
• Clinical Genetics
• Oncology

Background:

• Serrated polyposis syndrome (SPS) is the most common polyposis condition, characterized by multiple serrated polyps and increased colorectal cancer risk.
• The genetic basis of SPS is poorly understood, prompting recommendations for genetic testing to exclude other polyposis conditions.

Purpose of the Study:

• To evaluate the diagnostic yield of genetic testing in patients diagnosed with Serrated Polyposis Syndrome.
• To determine the utility of genetic testing in identifying underlying genetic causes or associated syndromes in SPS patients.

Main Methods:

• Retrospective analysis of patients meeting WHO criteria for SPS from a national referral center's Polyposis Registry.
• Inclusion of patients who underwent genetic testing (targeted or multigene panel) between April 2009 and February 2024.
• Extraction of genetic variant data from test reports and clinical information from medical records.

Main Results:

• Of 258 SPS patients tested, 119 had targeted gene testing and 139 had multigene panel testing.
• No pathogenic variants were found with targeted gene testing.
• Multigene panel testing identified pathogenic germline variants in 4 patients (2.9%), including three with Lynch syndrome (PMS2, MSH2) and one with an RNF43 variant.

Conclusions:

• Genetic testing showed a low diagnostic yield in this Serrated Polyposis Syndrome cohort.
• The findings suggest that undefined genetic factors or other pathophysiological mechanisms may be involved in SPS.
• Genetic testing appears to have limited utility for SPS diagnosis, primarily identifying incidental cases of Lynch syndrome.