Genetic Testing of Japanese Patients with Serrated Polyposis Syndrome: A Multicentric Study

Objectives: Serrated polyposis syndrome (SPS) is a rare condition associated with an increased risk of colorectal cancer. However, the genetic basis of SPS in Japanese patients remains unclear. The present study therefore aimed to address this omission by identifying candidate causative genes of SPS in Japanese patients.

Methods: The present study performed next-generation sequencing using a multigene panel to identify the causative genes in SPS. Whenever a candidate gene was detected, whole exome sequencing of the tumor tissue was performed.

Results: An analysis of 11 patients with SPS identified a germline pathogenic variant of BUB1 (c.1543G>T/p.Gly515Ter) in a 47-year-old, female patient with transverse colon cancer with more than 50 serrated polyps. She had no history of smoking. None of the canonical, causative genes in common colorectal cancer, such as APC, KRAS and TP53, were detected in her lesion. Most of the somatic variants detected in the cancer were transition substitutions (C>T).

Conclusions: BUB1 was identified as a candidate causative gene in SPS in a non-smoker with the disease. These findings will hopefully contribute to understanding the genetic basis of SPS.