高分辨率双能计算机断层扫描成像、无创（液体）活检和微创手术监测对 BAP1 肿瘤易感综合征患者间皮瘤早期检测的前瞻性评估

Background:

• Mutations involving BRCA1-Associated Protein-1 (BAP1), a nuclear deubiquitinase involved in epigenetic regulation of gene expression, DNA repair, and cellular energetics, have emerged as one of the most common somatic mutations in malignant mesotheliomas.
• Germline mutations involving BAP1 predispose individuals to mesothelioma as well as a variety of other malignancies including melanoma and lung, renal, gastric, breast, and biliary tract cancers.
• The cancer penetrance of germline BAP1 mutations is nearly 100%, with most patients developing multiple neoplasms.
• Presently there are no established guidelines for surveillance of cancer patients with germline BAP1 mutations or of cancer-free individuals with germline BAP1 mutations.

Objectives:

To prospectively gather information related to the use of dual energy computed tomographic imaging (DECT) together with minimally invasive surgical surveillance for early detection of pleural or peritoneal mesothelioma in participants with BAP1 tumor predisposition syndrome (TPDS)

Eligibility:

• Individuals with a history of any malignancy with known or suspected germline mutation involving BAP1.
• First- or second-degree relatives of patients with documented germline BAP1 mutations, who are also found to carry similar germline mutations.
• Age >= 30

Design:

• Participants with suspected hereditary tumor predisposition syndromes will undergo germline evaluation using CLIA-certified next-gen sequencing (NGS).
• First- and second-degree relatives of patients with germline BAP1 mutations who become protocol participants will be offered similar NGS evaluation.
• Participants with germline mutations in BAP1 will undergo periodic dual energy CT (DECT) scans of the chest, abdomen, and pelvis. Plasma cell-free DNA (cfDNA) will be assessed at similar intervals, and minimally invasive surveillance procedures (i.e., video-assisted thoracoscopy and laparoscopy) will be performed periodically to detect early, subclinical malignancies that may be amenable to potentially curative local interventions.