Prospective Evaluation of High Resolution Dual Energy Computed Tomographic Imaging, Noninvasive (Liquid) Biopsies, and Minimally Invasive Surgical Surveillance for Early Detection of Mesotheliomas in Patients With BAP1 Tumor Predisposition Syndrome

Background: A germline mutation is a change to a person s genes that is carried through their DNA. These mutations can be passed on from parents to their offspring. Germline mutations in a gene called BAP1 are linked to the development of mesothelioma and other cancers. Researchers want to follow people with these mutations to learn more. Objective: To see if researchers can improve how people who have or are suspected to have a BAP1 mutation are monitored over time. Eligibility: People age 30 and older who are suspected to have a BAP1 germline mutation. Design: Participants will be screened with a personal and family medical history. Their medical records may be reviewed. They will give a blood or saliva sample to test for a BAP1 mutation. They will get genetic counseling. To take part in this study, participants will enroll on 2 to 3 other protocols. Participants will have a physical exam. They may have a tumor biopsy. They will give blood and urine samples. They will have skin and eye exams. Some participants will have video-assisted thoracoscopy to examine the chest and lungs and diagnose suspicious areas. For this, a small camera is inserted into the chest through a small incision. Some participants will have laparoscopy to examine the organs inside the abdomen. For this, a small camera is inserted into the abdomen through a small incision. Participants will have imaging scans of the chest, abdomen, and pelvis. They may have brain scans. Participants will visit the NIH once a year for follow-up exams. Participation lasts indefinitely.

Sex

All

Minimum age

30 Years

Maximum age

120 Years

* ELIGIBILITY CRITERIA:

Inclusion Criteria for Genetic Testing

-Eligible participants include:

--Individuals with a history of any malignancy with known or suspected germline mutations involving BAP1

OR

--First- or second-degree relatives of patients (with or without cancer) with documented BAP1 tumor predisposition syndrome (TPDS)

* Age \>= 30 years.
* All participants must understand and be willing to sign a written informed consent document.

Inclusion Criteria for Surveillance

* Eligible participants include those who completed step 1 genetic testing with study-confirmed BAP1 or other germline TPDS mutation.
* Completed co-enrollment on protocol 06C0014, "Prospective Evaluation of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies."

• DERIVEDWu X, Hernandez FV, Wang H, Wang R, Shiffka S, Shah N, Carr SR, Hoang CD, Blakely AM, Lebensohn A, Mishra K, Xi S, Zhang MR, Tolunay T, Gara S, Absher A, Francis D, Rowland A, Connolly M, Jacobs S, Orfgen S, Driscoll K, Ghafoor A, Lu X, Malouf GG, Yang H, Carbone M, Hassan R, Jones E, Miettinen M, Schrump DS. Prospective Analysis of Mesotheliomas in Subjects With BAP1 Cancer Syndrome: Clinical Characteristics and Epigenetic Correlates of Disease. J Thorac Oncol. 2025 Nov;20(11):1699-1715. doi: 10.1016/j.jtho.2025.07.132. Epub 2025 Aug 6. PMID 40774608