Clinical and Histopathologic Characteristics of BAP1 Mutations

Study Overview
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Brief Summary
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The goal of this protocol is to determine the prevalence of somatic and germline mutations in BAP1 (BRCA associated protein-1) among patients with mesothelioma , choroidal nevus, primary uveal melanoma (UM), or metastatic UM seen at our institution.

Official Title
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Clinical and Histopathologic Characteristics of BAP1 Mutations

Conditions
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Malignant Pleural Mesothelioma (MPM), Choroidal Nevus, Primary Uveal Melanoma (UM), Metastatic Uveal Melanoma (UM), Renal Cell Carcinoma, Cholangiocarcinoma

Intervention / Treatment
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* Other: tumor specimens


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consents: > or = to 18 years of age Ability to provide informed consent Consent 1: Mesothelioma Histologically proven diagnosis of Mesothelioma OR Choroidal nevus Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography OR Primary uveal melanoma Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography Consent 2: Mesothelioma Histologically proven diagnosis of Mesothelioma AND BAP1 mutation or loss of expression identified in tumor sample OR one of the following: Age<50 at diagnosis No history of asbestos exposure Personal history of choroidal nevus, uveal melanoma, melanoma, renal cell carcinoma, or cholangiocarcinoma Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma History of malignancy in more than two first-degree relatives OR Choroidal nevus Diagnosis of choroidal nevus by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following: More than one clinical risk factor, which may include: orange pigment, thickness > 1 < 2.5mm Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma OR Primary uveal melanoma Diagnosis of uveal melanoma by direct examination and/or ultrasound/optical coherence tomography and possibly fluorescein angiography AND one of the following: Personal history of uveal melanoma, skin melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma Family history of choroidal nevus, uveal melanoma, mesothelioma, renal cell carcinoma, or cholangiocarcinoma History of malignancy in more than two first-degree relatives OR Metastatic uveal melanoma Histologically proven diagnosis of metastatic uveal melanoma AND BAP1 mutation or loss of expression identified in tumor sample OR one of the following: Personal history of uveal melanoma, skin melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma Family history of choroidal nevus, uveal melanoma, mesothelioma renal cell carcinoma, or cholangiocarcinoma History of malignancy in more than two first-degree relatives Consent 3: Relative of patient with germline BAP1 mutation identified through identified testing Exclusion Criteria: none

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| tissue<br>This is a protocol to obtain and/or analyze tumor and germline DNA specimens of patients with MPM, choroidal nevus, and UM. | Other: tumor specimens<br>* All consenting patients (Consent 1) will participate in an anonymized assessment of the prevalence of germline BAP1 mutations. Available tumor specimens from patients with MPM and metastatic uveal melanoma will be tested for BAP1 mutation. Patients whose tumors harbor BAP1 mutations and/or meet the criteria for germline mutation specified in 2.2.2 will be approached for identified germline BAP1 testing after appropriate pre-test counseling (Consent 2). Patients who, through identified testing, are found to have germline BAP1 mutations will be asked to invite their relatives to participate in germline testing (Consent 3). First-degree relatives and any relatives with a malignancy will be prioritized. Expanding testing to family members of patients with BAP1 germline mutations is essential to delineate the penetrance and describe the various manifestations of this new cancer predisposition syndrome.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine the prevalence of germline BAP1 mutations | Prevalence will be estimated as the proportion of all specimens who tested positive for mutation, and reported along with the corresponding exact 95% confidence intervals. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prevalence of somatic BAP1 mutations in disease mesothelioma and metastatic uveal melanoma. | The frequency of somatic mutations will be tabulated by factors of interest such as: personal and familial risk factors: age, smoking, and asbestos mesothelioma, personal and family history of cancer or of related diseases (mesothelioma and metastatic uveal melanoma) disease characteristics: histology, stage, location, site of metastasis (if present) (for mesothelioma and metastatic uveal melanoma); COMS criteria, GEP class, number of clinical risk factors (for metastatic uveal melanoma) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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somatic, germline, mutations, BAP1 (BRCA associated protein-1), 12-235