APC mosaicism, not always isolated: two first-degree relatives with apparently distinct APC mosaicism

APC mosaicism is briefly mentioned in the recently published BSG guidelines on hereditary colorectal cancer.1 We wish to present a family that underlines its relevance. A 26-year-old woman presented at the department of Clinical Genetics at Leiden University Medical Center with osteomas, lipomas, extra tooth and bowel problems. Using Sanger sequencing on leucocyte DNA, a pathogenic APC variant (NM_000038.6:c.4391_4394delAGAG) was detected with variant allele frequency of 20%–40%, indicating mosaicism. Subsequent colonoscopy and gastroduodenoscopy showed >200 colorectal adenomas in a patchy pattern and large variation in size and morphology, extended duodenal and gastric fundic gland polyposis. As summarised in table 1, targeted next-generation sequencing (NGS) on three adenomas and multiple normal tissues showed the same APC variant in all samples, suggesting an extensive mosaic pattern. Seven years earlier, her father presented with >40 colorectal adenomas without germline pathogenic APC or MUTYH variants. However, NGS on colorectal...

Source: Gut - October 6, 2023 Category: Gastroenterology Authors: Terlouw, D., Hes, F. J., Suerink, M., Boot, A., Langers, A. M. J., Tops, C. M., van Leerdam, M. E., van Asperen, C. J., Rozen, S. G., Bijlsma, E. K., van Wezel, T., Morreau, H., Nielsen, M. Tags: Gut PostScript Source Type: research