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Letter
APC mosaicism, not always isolated: two first-degree relatives with apparently distinct APC mosaicism
  1. Diantha Terlouw1,2,
  2. Frederik J Hes3,
  3. Manon Suerink1,
  4. Arnoud Boot4,
  5. Alexandra M J Langers5,
  6. Carli M Tops1,
  7. Monique E van Leerdam5,
  8. Christi J van Asperen1,
  9. Steve G Rozen4,
  10. Emilia K Bijlsma1,
  11. Tom van Wezel2,
  12. Hans Morreau2,
  13. Maartje Nielsen1
  1. 1 Department of Clinical Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  2. 2 Department of Pathology, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  3. 3 Centre for Medical Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
  4. 4 Department of Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore
  5. 5 Department of Gastroenterology and Hepatology, Leids Universitair Medisch Centrum, Leiden, The Netherlands
  1. Correspondence to Dr Maartje Nielsen, Department of Clinical Genetics, Leiden University Medical Center, Leiden 2300 RC, The Netherlands; m.nielsen{at}lumc.nl

https://doi.org/10.1136/gutjnl-2022-328540

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    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.

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    Table 1

    Overview of all tissues tested with NGS and variant allel frequencies of the detected mosaic variant

    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) …

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    Footnotes

    • 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.