Patient case: 26-year-old female with chondrosarcoma; genetic feature: IDH1

Clinical trial: Long Term Follow-up of Mesothelioma Patients and Their Family Members With Germline Mutations in BAP1 and Other Genes

Summary: Background:
  -A gene provides instructions to the body. Mutated genes can sometimes cause cancer. Germline mutations are those people are born with. These mutations in the BAP1 gene can cause mesothelioma and other cancers. Researchers want to study people with germline mutations of BAP1 and other genes known to cause cancer.
  Objective:
  -To learn how cancer might develop in people with certain gene mutations.
  Eligibility:
  -People ages 2 and older with a germline mutation in BAP1 or another gene that might cause cancer
  Design:
  -  Participants will be screened with:
  -  Medical and family history
  -  Saliva test
  -  Participants with mesothelioma will be in the NIH Group. Participants without mesothelioma can choose to be in either the NIH Group or the Remote Group.
  -  Remote Group participants will have a medical and family history by phone. If they have tumor tissue from a previous surgery, it will be tested. They will be contacted once a year by phone.
  -  NIH Group participants will have a baseline visit. This can take up to 4 days. They may have to stay in the area overnight. The visit will include:
  -  Physical exam
  -  Evaluation of tumor tissue if available
  -  Optional tumor biopsy
  -  Blood tests
  -  Scans: A machine will take pictures of the body.
  -  Photographs of skin lesions or other issues
  -  Skin exam
  -  Eye exam
  -  NIH Group participants will have visits once or twice a year. These will include a physical exam, lab tests, scans, and other tests as needed.
  -  Participants who have a confirmed mutation will be asked to contact any relatives who may be at risk and ask them about joining the study.

Detailed description: 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 malignant mesothelioma patients and their family members who have germline mutations in BAP1 and other DNA repair/cancer predisposition genes
  Eligibility for Genetic Testing:
  Cohort 1
  -Individual with mesothelioma with deleterious germline mutations in BAP1 or another DNA-repair/cancer predisposition gene(s) (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 greater than or equal to 2 years old
  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 confirmed germline mutation in BAP1
  OR
  --a first degree biological relative with mesothelioma and a CLIA confirmed germline mutation in another DNA-repair/cancer predisposition genes
  OR
  --a second degree biological relative with mesothelioma and a CLIA confirmed germline mutation in BAP1
  -Age greater than or equal to 16 unless participant has a first degree biological relative with a confirmed p53 germline mutation; in such cases, will begin screening at age greater than or equal to 2 years old.
  Eligibility for Surveillance:
  Cohort 1
  -No additional criteria
  Cohort 2
  -Testing performed on study must confirm presence of germline mutation in BAP1 or another DNA repair/cancer predisposition gene(s)
  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 as well as other mutations involved in DNA repair.
  -  Screening examinations will be offered to those with germline BAP1 mutations as well as other mutations involved in DNA repair/cancer predispositoin.
  -  We will determine if there is a relationship between germline mutation and disease phenotype.

Eligibility: -  Inclusion Criteria:
  Inclusion Criteria for Genetic Testing:
  Cohort 1:
  -  Subject with pathology confirming a diagnosis of mesothelioma.
  -  Subject must have a deleterious germline BAP1 mutation. Results from either research or clinical analyses are sufficient for this criterion.
  OR
  -Subject with mesothelioma otherwise eligible for genetic testing in Cohort 2
  OR
  -  Subject must have deleterious germline mutation in another DNA repair/cancer predisposition gene(s). Results from either research or clinical analyses are sufficient for this criterion.
  -  Age greater than or equal to 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 either:
  ---A biological first degree relative (living or deceased) with a history of mesothelioma
  OR
  ---A first degree biological relative with a CLIA confirmed germline mutation in BAP1
  OR
  ---A first degree biological relative with mesothelioma and a CLIA confirmed germline mutation in another DNA-repair/cancer predisposition gene.
  OR
  -  A second degree biological relative with mesothelioma and a CLIA confirmed germline mutation in BAP1)
  -Age:
  -  Greater than or equal to 2 years for subjects with a first degree relative that has a germline mutation in p53
  -  Greater than or equal to 16 years for all other eligible potential mutations
  -  All participants or their legally authorized representatives (LARs) must understand and be willing to sign a written informed consent
  Inclusion Criteria for Surveillance:
  -  Genetic testing criteria for respective cohorts must be met
  -  Subjects in Cohort 1 may be enrolled with positive results for germline BAP1 mutation or another DNA repair/cancer predisposition gene(s) regardless of CLIA confirmation
  -  Subjects in Cohort 2 must have CLIA confirmed germline BAP1 mutation or another DNA repair/cancer predisposition gene(s)

Relevance to patient case: not relevant