Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

March 5, 2026 updated by: Mohamed Abdel-Rahman
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.

Study Overview

Status

Recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Providers at OSU will identify eligible participants through clinical practice. Providers at other institutions who become aware of our research through presentations at conferences, publications, etc. may identify one of their patients as eligible or potentially eligible for the study and introduce the study to their patient.

Description

Inclusion Criteria:

Patients who meet any of the following criteria:

  1. 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.
  2. Any patient with personal history of at least 2 cancers reported in hereditary BAP1 cancer predisposition syndrome.
  3. Any subject (affected or unaffected) with a documented BAP1 pathogenic/ likely pathogenic variant.
  4. Any patient with a cancer reported in BAP1 and a germline variant of uncertain significance.
  5. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Family-Based
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Patients with personal and/or family history suggestive of hereditary BAP1
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, hepatocellular carcinoma and meningioma
Pathogenic, likely pathogenic variants in BAP1 and variants of uncertain significance

Affected and unaffected individuals with pathogenic or likely pathogenic variant in BAP1 and their family members

Patients with personal family history of any of the BAP1 associated cancer and a variant of uncertain significance of BAP1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of germline BAP1 variants in the unselected general population of cancer patients
Time Frame: 5 years
Frequency of germline BAP1 pathogenic/likely pathogenic variants in different cancers
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
Questionnaire and chart review of the clinical phenotype
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Questionnaire to assess environmental risk factors modifying cancer risk in patients
Time Frame: 10 years
Measurement used: questionnaire for various environmental risk factors
10 years
Genotyping to assess genetic risk factors modifying risk of cancer
Time Frame: 10 years
Genotyping for genetic variants that could modify the risk of cancer in subjects.
10 years
Disease outcome (response to treatment, prognosis including prognostic markers)
Time Frame: 10 years
Chart review of disease outcome
10 years
Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations)
Time Frame: 10 years
Review of pathology and study of genomics alterations in tumors
10 years
Assessment of disease penetrance and life time risk estimate
Time Frame: 10 years
Statistical assessment of disease penetrance and life time risk estimates of various cancers
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mohamed Abdel-Rahman

Investigators

  • Principal Investigator: Mohamed H Abdel-Rahman, MD, PhD, Ohio State University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2015

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

March 7, 2021

First Submitted That Met QC Criteria

March 7, 2021

First Posted (Actual)

March 11, 2021

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 5, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014C0072

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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