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Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer.

ABSTRACT: Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift BAP1 variant, and as expected, immunostaining validated the loss of BAP1 protein in patient-derived tumor specimens. Together, these data provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of the BAP1 TPDS continues to evolve, and may affect future screening and surveillance guidelines.

SUBMITTER: Tesch ME

PROVIDER: S-EPMC7089973 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer.

Tesch Megan E ME Pater Justin A JA Vandekerkhove Gillian G Wang Gang G Binnington Kristin K So Alan I AI Wyatt Alexander W AW Eigl Bernhard J BJ

NPJ genomic medicine 20200323

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift BAP1</ ...[more]

PMID: 32218990

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Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer

Project description:Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1-tumor predisposition syndrome (BAP1-TPDS). BAP1-TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a novel germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. A concurrently identified somatic frameshift BAP1 variant and the predicted deleterious effects of the germline BAP1 variant provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of BAP1-TPDS continues to evolve and may affect future screening and surveillance guidelines.

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Saturation genome editing of BAP1 functionally classifies somatic and germline variants.

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Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas.

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Are Pathogenic Germline Variants in Metastatic Melanoma Associated with Resistance to Combined Immunotherapy?

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