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- colorectal adenomas
- colorectal cancer
- colorectal cancer genes
- familial adenomatous polyposis
- gastrointestinal pathology
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 adenomas showed another mosaic APC variant (NM_000038.6:c.3712_3713delAG) …
Contributors DT: acquisition of data, analysis and interpretation of data, drafting of the manuscript. FH, MS: acquisition of data, critical revision of the manuscript. AB, SR: providing mutational signature knowledge, critical revision of manuscript. AMJL: acquisition of clinical data, interpretation of data, critical revision of the manuscript. CT, MEvL: interpretation of data, critical revision of manuscript. CJvA: acquisition of clinical data, revision of manuscript. EKB: providing probability measurement knowledge, critical revision of manuscript. TvW, HM and MN: study concept and design, obtained funding, analysis and interpretation of data, critical revision of the manuscript.
Funding This study is supported by the Dutch Cancer Society, project number: 11292.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.