Dataset Information

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases.

ABSTRACT: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a recently identified hereditary cancer syndrome. Germline mutations in this tumor suppressor gene predispose families to the development of various malignancies. The molecular functions of the gene as well as the clinical phenotype of the syndrome are still being clarified. We sought to conduct a comprehensive review of published research into BAP1-TPDS to more thoroughly delineate the clinical implications of germline BAP1 mutations. We also report two additional families with germline BAP1 mutations. Current evidence demonstrates that germline BAP1 mutations predispose families to uveal melanoma, renal cell carcinoma, malignant mesothelioma, cutaneous melanoma, and possibly to a range of other cancers as well. Some of these cancers tend to be more aggressive, have a propensity to metastasize, and onset earlier in life in patients with BAP1 mutations as compared to non-predisposed patients with equivalent cancers. Although further research is necessary, this information can aid in the management, diagnosis, and therapy of these patients and their families, and highlights the importance of genetic counseling.

SUBMITTER: Rai K

PROVIDER: S-EPMC4688243 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases.

Rai K K Pilarski R R Cebulla C M CM Abdel-Rahman M H MH

Clinical genetics 20150714 3

The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a recently identified hereditary cancer syndrome. Germline mutations in this tumor suppressor gene predispose families to the development of various malignancies. The molecular functions of the gene as well as the clinical phenotype of the syndrome are still being clarified. We sought to conduct a comprehensive review of published research into BAP1-TPDS to more thoroughly delineate the clinical implications of ge ...[more]

PMID: 26096145

Similar Datasets

Project description:ImportancePatients with germline mutations in BAP1 may develop several flesh-colored melanocytic BAP1-mutated atypical intradermal tumors (MBAITs). These tumors generally develop earlier than other BAP1-associated tumors, highlighting an important role for dermatologists in identifying and screening patients with a history suggestive of a germline mutation.ObjectiveTo describe 8 new families with germline mutations in BAP1 and provide a comprehensive review of reported cases.Design, settings and participantsPatients were identified in an outpatient dermatology clinical setting over a 6-month period (10 mutation carriers from 8 families) and through a literature review using PubMed (205 patients).ExposuresMutations were identified through next-generation sequencing of saliva or blood samples, and RNA was extracted from fibroblasts cultured from a patient with an intronic variant to determine the impact of the mutation on the coding sequence.Main outcomes and measuresAll 215 patients were assessed for personal and/or family history and genotype. These findings were compiled and assessed for any association between genotype and phenotype.ResultsOverall, this study included 215 patients (108 women, 91 men, and 16 gender unspecified; median [range] age, 46.5 [10.0-79.0] years). Nine of the 10 patients who were identified in the outpatient dermatology setting were found to have MBAITs on clinical examination. Forty of 53 patients (75%) identified in the literature review who underwent total-body skin examinations (TBSE) were found to have MBAITs, suggesting a high penetrance in patients who have undergone TBSE. The most prevalent malignancies among BAP1 mutation carriers were uveal melanoma (n?=? 60 [28%]), mesothelioma (n?=?48 [22%]), cutaneous melanoma (n?=?38 [18%]), and renal cell carcinoma (n?=?20 [9%]). A total of 71 unique mutations in BAP1 have been reported.Conclusions and relevanceOur results indicate that germline mutations in both coding and noncoding regions throughout the BAP1 gene can impair protein function, leading to an increased risk for several associated malignancies. Four of the 8 probands we present had no history of BAP1-associated malignancies and were assessed for germline mutations when found to have MBAITs on dermatologic examination. Dermatologists can identify patients with a high likelihood of the BAP1 cancer syndrome through personal and family history and TBSE for the presence of possible MBAITs.

Dataset Information

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases.

Publications

Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets