Groups/Cohorts: tissueThis is a protocol to obtain and/or analyze tumor and germline DNA specimens of patients with MPM, choroidal nevus, and UM.Assigned Interventions: Other: tumor specimensAll 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.
Primary Outcome Measures:
- determine the prevalence of germline BAP1 mutations
- [ Time Frame: 2 years ]
- [ Designated as safety issue: No ]
- 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.
Secondary Outcome Measures:
- prevalence of somatic BAP1 mutations in disease MPM and metastatic uveal melanoma.
- [ Time Frame: 2 years ]
- [ Designated as safety issue: No ]
- The frequency of somatic mutations will be tabulated by factors of interest such as:
- personal and familial risk factors: age, smoking, and asbestos (MPM), personal and family history of cancer or of related diseases (MPM and metastatic uveal melanoma)
- disease characteristics: histology, stage, location, site of metastasis (if present) (for MPM and metastatic uveal melanoma); COMS criteria, GEP class, number of clinical risk factors (for metastatic uveal melanoma)
Eligibility Criteria
- Inclusion Criteria:
- All consents:
- > or = to 18 years of age
- Ability to provide informed consent
- Consent 1: malignant pleural mesothelioma (MPM)
- Histologically proven diagnosis of MPM 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: MPM
- Histologically proven diagnosis of MPM 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, or melanoma
- Family history of choroidal nevus, uveal melanoma, or mesothelioma
- 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, or mesothelioma
- Family history of choroidal nevus, uveal melanoma, or mesothelioma 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, or mesothelioma
- Family history of choroidal nevus, uveal melanoma, or mesothelioma
- 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, or mesothelioma
- Family history of choroidal nevus, uveal melanoma, or mesothelioma
- 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
