Germline mutations in BRCA1 associated protein 1 (BAP1) are associated with unique disease profiles in mesothelioma, atypical spitz nevi, and uveal melanoma, but the patient characteristics of an unselected population of BAP1 carriers identified by an ascertainment prevalence study are unknown.
In total, eight patients (4.7%) had pathogenic alterations in BAP1 with the highest frequencies of in patients with a personal/family history of ≥2 BAP1-related cancers 6/16 (38%), age of onset <35 years 4/21 (19%) and familial UM 6/34 (18%).
Uveal melanoma (UM), a rare cancer of the eye, is characterized by initiating mutations in the genes G-protein subunit alpha Q (<i>GNAQ</i>), G-protein subunit alpha 11 (<i>GNA11</i>), cysteinyl leukotriene receptor 2 (<i>CYSLTR2</i>), and phospholipase C beta 4 (<i>PLCB4</i>) and by metastasis-promoting mutations in the genes splicing factor 3B1 (<i>SF3B1</i>), serine and arginine rich splicing factor 2 (SRSF2), and BRCA1-associated protein 1 (<i>BAP1</i>).
Unilateral multifocal uveal melanoma in the absence of ocular melanocytosis appears to occur preferentially in tumors with the class 2 gene expression profile and a BRCA1-associated protein 1 gene (BAP1) mutation.
As our BCCs probably developed independently from the BAP1-TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.
Concluding, vascular density of UM relates to its genetic profile: Monosomy 3 and BAP1-loss are associated with an increased MVD, while an early event (gain of 8q) is not independently related to MVD, but may initiate a preparation phase towards development of vessels.
Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma.
We have used the "Calling Card System" of transposase-directed transposon insertion mapping to identify the genomic targets of BAP1 in uveal melanoma (UM).
The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors.
Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers.
Germline pathogenic variants in BRCA1-associated protein-1 (BAP1), a nuclear ubiquitin carboxy-terminal hydrolase with evidence suggestive of independent tumor suppressor function, predispose affected families to uveal melanoma, cutaneous melanoma, renal cell carcinoma, malignant mesothelioma, and possibly a range of other tumors and malignancies as part of the BAP1 tumor predisposition syndrome, a recently recognized hereditary cancer syndrome.