Long Term Follow-Up of Patients With Mesothelioma and Individuals With Germline Mutations in BAP1

Background:

• BRCA1-Associated Protein-1 (BAP1), a deubiquitinase involved in regulating DNA repair enzymes, is believed to be a prominent mutation in malignant mesothelioma.
• Germline mutations involving BAP1 have been reported in familial studies. These have been associated with a higher likelihood of mesothelioma as well as several other malignancies, including uveal melanoma, cutaneous melanomas, renal cell carcinoma and cholangiocarcinoma.
• BAP1 mutations, if found, have a high probability of detecting multiple malignancies in family members.

Objectives:

-To characterize the natural and clinical history of patients with malignant mesothelioma, their family members and individuals who have germline mutations in BAP1

Eligibility for Genetic Testing:

Cohort 1

-Individual with mesothelioma with deleterious germline mutations in BAP1 (previous testing may have been research or clinical)

OR

• Individual with a diagnosis of mesothelioma who is otherwise eligible for testing on Cohort 2
• Age >= 2

Cohort 2

-Individual with a germline BAP1 mutation who does not have a history of mesothelioma (previous testing may have been research or clinical)

OR

-Individual with no personal history of mesothelioma with:

--a first degree biological relative (living or deceased) with a history of mesothelioma

OR

--a first degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1

OR

--a second degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1 if relevant first degree relative is deceased or unavailable for testing

OR

--a second degree biological relative with mesothelioma and a CLIA (or equivalent) confirmed germline mutation in BAP1

-Age >= 2

Eligibility for Surveillance:

Cohort 1

-No additional criteria

Cohort 2

-Testing performed on study must confirm presence of germline mutation in BAP1

Design:

• Individuals with suspected hereditary predisposition to mesothelioma and their families will be recruited to assess for genetic mutations, and to study the natural history of malignancies occurring in germline BAP1 mutations.
• Screening examinations will be offered to those with germline BAP1 mutations.
• We will determine if there is a relationship between germline mutation and disease phenotype.

• Inclusion Criteria for Genetic Testing:

Cohort 1:

• Participant with pathology confirming a diagnosis of mesothelioma.
• Participant must have a deleterious germline BAP1 mutation. Results from either research or clinical analyses are sufficient for this criterion.

OR

• Participant with mesothelioma otherwise eligible for genetic testing in Cohort 2
• Age >= 2 years

Cohort 2:

-Individual with a germline BAP1 mutation who does not have a history of mesothelioma (other cancers are allowed). Results from either research or clinical analyses are sufficient for this criterion.

OR

-Individual with no history of mesothelioma with:

--A biological first degree relative (living or deceased) with a history of mesothelioma

OR

--A first degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1

OR

--A second degree biological relative with a CLIA (or equivalent) confirmed germline mutation in BAP1 if relevant first degree relative is deceased or unavailable for testing,

OR

--A second degree biological relative with mesothelioma and a CLIA (or equivalent) confirmed germline mutation in BAP1

-Age >= 2 years

All participants must understand and be willing to sign a written informed consent

Exclusion criteria

for Genetic Testing

None

Inclusion criteria

for Surveillance:

Inclusion criteria

for Surveillance

• Genetic testing criteria including age restrictions for respective cohorts must be met.
• Participants in Cohort 1 may be enrolled with positive results for germline BAP1 mutation regardless of CLIA (or equivalent) confirmation
• Participants in Cohort 2:

• must have CLIA (or equivalent) confirmed germline BAP1 mutation

Exclusion criteria

for Surveillance

None