Clinical trial NCT04792463: Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
Official title: Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Uveal Melanoma
Cutaneous Melanoma
BAP1 Gene Mutation
Renal Cell Carcinoma
Mesothelioma
Hepatocellular Carcinoma
Cholangiocarcinoma
Meningioma Atypical
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2021-03-11
Enrollment: 500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of germline BAP1 variants in the unselected general population of cancer patients
timeFrame: 5 years
measure: Clinical phenotypes (this includes premalignant lesions, tumor type and age of onset) in at risk blood-line family members of the patients
timeFrame: 5 years
Secondary outcomes:
measure: Questionnaire to assess environmental risk factors modifying cancer risk in patients
timeFrame: 10 years
measure: Genotyping to assess genetic risk factors modifying risk of cancer
timeFrame: 10 years
measure: Disease outcome (response to treatment, prognosis including prognostic markers)
timeFrame: 10 years
measure: Tumor pathology and genomics (including tumor grade, stage, somatic genomic alterations)
timeFrame: 10 years
measure: Assessment of disease penetrance and life time risk estimate
timeFrame: 10 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Mohamed H Abdel-Rahman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: