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NCT Number: NCT04792463

Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome

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.

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Key information

Conditions

Uveal Melanoma Adenocarcinoma Adenoma BAP1 Gene Mutation Carcinoma Carcinoma, Hepatocellular Carcinoma, Renal Cell Cholangiocarcinoma Cutaneous Melanoma Digestive System Diseases Digestive System Neoplasms Eye Diseases Eye Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hepatocellular Carcinoma Kidney Diseases Kidney Neoplasms Liver Diseases Liver Neoplasms Male Urogenital Diseases Melanoma Meningioma Atypical Mesothelioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Renal Cell Carcinoma Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uveal Diseases Uveal Neoplasms

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. Questionnaire to assess environmental risk factors modifying cancer risk in patients

    Time frame: 10 years

    Measurement used: questionnaire for various environmental risk factors

  2. 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.

  3. Disease outcome (response to treatment, prognosis including prognostic markers)

    Time frame: 10 years

    Chart review of disease outcome

  4. 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

  5. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Mohamed H Abdel-Rahman, MD, PhD

CONTACT

[email protected]

614-292-1396

Sponsors and collaborators

Lead sponsor

Mohamed Abdel-Rahman

Other

Registry information

Important dates

Study start
2015
Primary completion
2026
Study completion
2026
First posted
Mar 11, 2021
Registry last updated
Mar 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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