Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Uveal Melanoma, Cutaneous Melanoma, BAP1 Gene Mutation, Renal Cell Carcinoma. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This research will have a significant impact on the overall management of those cancer patients and their family members who are at risk for hereditary cancer due to germline inactivation of BAP1. Our study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. Because the vast majority of UM develop in pre-existing nevi, characterization of individuals at high risk for development of UM will allow closer screening and earlier intervention which would improve the treatment outcome not only for retaining vision but also for overall survival. Similarly in patients with germline BAP1 mutation CM develops in premalignant atypical melanocytic lesions and careful follow up of these patients will improve the outcome of their disease. In addition this study could have impact on the management of patients with personal and/or family history of several other cancers reported in patients with germline BAP1 mutation such as mesothelioma, renal cell carcinoma, cholangiocarcinoma, hepatocellular carcinoma, meningioma and basal cell carcinoma.
Detailed description
BAP1 (BRCA1-associated protein-1), is a deubiquitinating enzyme with a ubiquitin carboxy-terminal hydrolase function that has been suggested to be a tumor suppressor gene with a role in cell proliferation and growth inhibition. Recently germline mutations in BAP1 have been identified by our group and others in families with hereditary cancers. However, the clinical spectrum of cancers in patients with germline BAP1 is still not clear. The association of germline BAP1 mutations with increased risks for uveal melanoma (UM), mesothelioma, cutaneous melanoma (CM), renal cell carcinoma (RCC) and BAP1-inactivated melanocytic tumors is fairly well established. However, several other cancers have been reported in these patients and their family members including cholangiocarcinoma, hepatocellular carcinoma, meningioma, basal cell carcinoma and other internal malignancies. Identification of the clinical phenotype of BAP1-TPDS is important for proper counseling and management of patients.
Primary outcome measures
- Prevalence of germline BAP1 variants in the unselected general population of cancer patients [Time frame: 5 years]
- Clinical phenotypes (this includes premalignant lesions, tumor type and age of onset) in at risk blood-line family members of the patients [Time frame: 5 years]
Secondary outcome measures (5)
- Questionnaire to assess environmental risk factors modifying cancer risk in patients [Time frame: 10 years]
- Genotyping to assess genetic risk factors modifying risk of cancer [Time frame: 10 years]
- Disease outcome (response to treatment, prognosis including prognostic markers) [Time frame: 10 years]
- Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations) [Time frame: 10 years]
- Assessment of disease penetrance and life time risk estimate [Time frame: 10 years]
Eligibility criteria
Inclusion criteria
Patients who meet any of the following criteria:
- Personal history of one cancer reported in BAP1 cancer predisposition syndrome and family history of at least two 1st or 2nd degree relatives with cancer reported in hereditary BAP1 cancer predisposition syndrome such as UM, CM, mesothelioma, RCC, cholangiocarcinoma, meningioma and hepatocellular carcinoma.
- Any patient with personal history of at least 2 cancers reported in hereditary BAP1 cancer predisposition syndrome.
- Any subject (affected or unaffected) with a documented BAP1 pathogenic/ likely pathogenic variant.
- Any patient with a cancer reported in BAP1 and a germline variant of uncertain significance.
- At risk relatives of a patient with documented BAP1 mutation.
Exclusion criteria
- Study material including consent forms are currently only available in English so non-English speaking subjects are excluding
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Family-based
Study locations
United States · 1 center
- The Ohio State University Wexner Medical Center — Columbus
Publications
- Godwin K, McElroy J, Senter L, Byrne L, Abdel-Rahman MH. Patient-derived outcome assessment of knowledge, communication, and management in those diagnosed with BAP1-tumor predisposition syndrome. Fam Cancer. 2026 Mar 17;25(2):28. doi: 10.1007/s10689-026-00541-8. PMID 41843333
Identifiers
NCT: NCT04792463 · 2014C0072