Frequency of somatic mosaicism in the APC gene in patients with adenomatous

Background: Adenomatous polyposes of the colon are systemic procesess, which lead to the development of a large number of colorectal (CR) polyps. Hereditary adenomatous polyposes are a genetically heterogeneous group, caused by pathogenic variants/likely pathogenic variants (PV /LPV) in various genes with different modes of inheritance. Hereditary adenomatous polyposes are the cause of approximately I% of CR cancers. Somatic mosaicism occurs as a result of a genetic change taking place after the first zygotic division leading to the presence of different genetic variants in different cells of the body. According to available literature, somatic APC mosaicism is expected to be the cause of as much as 20% of adenomatous polyposes cases with negative family history. It is also likely that in routine clinical practice somatic APC mosaicism is underestimated as a cause of adenomatous polyposis and CR cancers. Numerous cases of somatic mosaicism for hereditary cancer predispositions go undiagnosed due to a lack of referral to genetic counseling in patients with a negative family history. 

Patients and methods: In this study we will include 75 patients with IO or more colorectal adenomatous polyps, who have a negative genetic test for germline PV/LPV in genes associated with adenomatous polyposis of the colon. Testing (genotyping) will be performed on two polyp tissue samples from each patient, acquired during a past colonoscopy examination, using next generation sequencing on the sequenator NextSeq 550. 

Aim: To determine the proportion of patients in whom somatic APC mosaicism is the cause of colorectal adenomatous polyps; in this study we will include patients with 10 or more colorectal adenomatous polyps, who have a negative genetic test for germline PV/LPV in genes associated with adenomatous polyposis of the colon.