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Case Reports
. 2025 Jul 10:e64176.
doi: 10.1002/ajmg.a.64176. Online ahead of print.

First Report of BAP1-Associated Polyposis

Angela L Jacobson  1 , Maegan E Roberts  2 , Lindsey Byrne  2 , Jenna Wolfe  2 , Peter P Stanich  3 , Mohamed H Abdel-Rahman  4 , Colin C Pritchard  1 , Eric Q Konnick  1   5
Affiliations
Case Reports

First Report of BAP1-Associated Polyposis

Angela L Jacobson et al. Am J Med Genet A. .

Abstract

BAP1 Tumor Predisposition Syndrome (BAP1-TPDS) is caused by germline pathogenic variants in the BAP1 gene and has been associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other benign cutaneous lesions. Adenomatous colon polyposis has not previously been reported as part of BAP1-TPDS. We report two patients with unexplained adenomatous oligopolyposis and germline BAP1 pathogenic variants. To determine if BAP1 had a role in polypogenesis, we performed somatic mutational analysis on multiple polyps from both patients (n = 8 total polyps tested). In every polyp tested, we found evidence of second BAP1 allele inactivation, including second somatic BAP1 mutations. Further, we did not detect any mutations in the commonly identified adenomatous polyposis pathway drivers, APC, CTNNB1, or other WNT/β-catenin. We did not detect somatic BAP1 mutations in any adenomatous polyps from patients without germline BAP1 pathogenic variants (n = 151 patients), highlighting the specificity of somatic BAP1 second hit mutations in BAP1 germline carrier polyps. Our findings strongly support that the polyps in these patients were caused by BAP1, and that adenomatous oligopolyposis is a part of the BAP1-TPDS tumor spectrum. Further work is needed to characterize the penetrance of this new BAP1-associated phenotype.

Keywords: BAP1; BAP1‐TPDS; adenomas; adenomatous polyposis; germline; polyps.

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References

    1. Abdel‐Rahman, M. H., R. Pilarski, C. M. Cebulla, et al. 2011. “Germline BAP1 Mutation Predisposes to Uveal Melanoma, Lung Adenocarcinoma, Meningioma, and Other Cancers.” Journal of Medical Genetics 48, no. 12: 856–859. https://doi.org/10.1136/jmedgenet‐2011‐100156.
    1. de la Fouchardière, A., O. Cabaret, L. Savin, et al. 2015. “Germline BAP1 Mutations Predispose Also to Multiple Basal Cell Carcinomas.” Clinical Genetics 88, no. 3: 273–277. https://doi.org/10.1111/cge.12472.
    1. Dos Santos, W., M. B. Dos Reis, J. Porto, et al. 2022. “Somatic Targeted Mutation Profiling of Colorectal Cancer Precursor Lesions.” BMC Medical Genomics 15, no. 1: 143. https://doi.org/10.1186/s12920‐022‐01294‐w.
    1. Huang, K.‐L., R. J. Mashl, Y. Wu, et al. 2018. “Pathogenic Germline Variants in 10,389 Adult Cancers.” Cell 173, no. 2: 355–370.e14. https://doi.org/10.1016/j.cell.2018.03.039.
    1. Shankar, G. M., M. Abedalthagafi, R. A. Vaubel, et al. 2017. “Germline and Somatic BAP1 Mutations in High‐Grade Rhabdoid Meningiomas.” Neuro‐Oncology 19, no. 4: 535–545. https://doi.org/10.1093/neuonc/now235.

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