First Report of BAP1-Associated Polyposis
Angela L Jacobson1, Maegan E Roberts2, Lindsey Byrne2
1Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
American Journal of Medical Genetics. Part A
|July 10, 2025
Summary
Adenomatous colon polyposis is now recognized as part of BAP1 Tumor Predisposition Syndrome (BAP1-TPDS). Germline BAP1 variants lead to polyps through second BAP1 allele inactivation, expanding the BAP1-TPDS tumor spectrum.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- BAP1 Tumor Predisposition Syndrome (BAP1-TPDS) is linked to germline pathogenic variants in the BAP1 gene.
- Associated cancers include uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma.
- Adenomatous colon polyposis has not been previously reported in BAP1-TPDS.
Observation:
- Two patients presented with unexplained adenomatous oligopolyposis and germline BAP1 pathogenic variants.
- Somatic mutational analysis was performed on polyps from these patients.
- Evidence of second BAP1 allele inactivation, including somatic mutations, was found in all tested polyps.
Findings:
- Second somatic BAP1 mutations were identified in every polyp analyzed.
- No mutations were detected in common adenomatous polyposis pathway drivers (APC, CTNNB1, WNT/β-catenin).
- Somatic BAP1 mutations were specific to polyps from BAP1 germline carriers, unlike 151 patients without germline BAP1 variants.
Implications:
- These findings strongly implicate BAP1 as the cause of polyps in these patients.
- Adenomatous oligopolyposis is now considered a BAP1-TPDS tumor spectrum phenotype.
- Further research is required to determine the penetrance of this newly identified BAP1-associated condition.
