Clinical and Histopathologic Characteristics of BAP1 Mutations

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01773655

Collaborator

United States Department of Defense (U.S. Fed)

196

Enrollment

Locations

89.9

Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Mesothelioma (MPM) Choroidal Nevus Primary Uveal Melanoma (UM) Metastatic Uveal Melanoma (UM) Renal Cell Carcinoma Cholangiocarcinoma	Other: tumor specimens

Study Design

Study Type:

Observational

Actual Enrollment :

196 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical and Histopathologic Characteristics of BAP1 Mutations

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Jun 30, 2020

Actual Study Completion Date :

Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
tissue 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 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.

Arm

Intervention/Treatment

tissue

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

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.

Outcome Measures

Primary Outcome Measures

determine the prevalence of germline BAP1 mutations [2 years]
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 mesothelioma and metastatic uveal melanoma. [2 years]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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