Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Syndrome

Mesothelioma

Mesothelioma, Malignant

Disease Susceptibility

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Disease Attributes

Malignant Mesothelioma

BAP1 Tumor Predisposition Syndrome

Individuals with history of cancer and detected or suspected germline mutation in BAP1 TPDS

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

Deneise Francis, R.N.

David S Schrump, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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.

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 patients 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 greater than or equal to 30

Design:

* Individuals 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 will be offered similar NGS evaluation.
* Subjects 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.

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

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Documentation of the counts, incidence, and frequencies of cancers from dual energy computed tomographic imaging and minimally invasive surveillance results will be analyzed for statistical analysis for the early detection of mesotheliomas in patients with BAP1 TPDS.

Characterization of the epigenetic features of mesotheliomas associated with germline mutations in BAP1.

Tumor tissue, blood, saliva, or buccal swab specimen for genetic analyses including WES, FACS, Western blots, and RNA sequencing.

National Cancer Institute (NCI)

Digestive System Diseases

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Adenocarcinoma

Stomach Neoplasms

Breast Neoplasms

Neoplastic Syndromes, Hereditary

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Diffuse Gastric Cancer

Hereditary Diffuse Gastric Cancer

Subjects with suspicious personal or family medical history of gastric cancer or gastric cancer syndrome.

Jamie Kirkpatrick, R.N.

Jeremy L Davis, M.D.

Background:

Gastric cancers are cancers of the stomach. Hereditary ones are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. They want to learn about changes these cause in the body and about the genes involved.

Objective:

-To gather data about hereditary gastric cancer.

Eligibility:

* People at least 2 years old with personal or family history with a hereditary gastric cancer.
* People at least 2 years old with gene changes that lead to such cancer or a lesion that may be hereditary.

Design:

* Participants will be screened in a separate protocol.
* Participants will have:

  * Physical exam
  * Medical history
  * Blood tests
  * Scans
  * Photos of skin lesions and other findings
  * Gynecology consultation for women
  * Cheek swab (some participants)
* For some participants, their relatives will be asked to join the study.
* Some participants will be asked to allow the study to get stored tissue samples for relatives who have died.
* Some samples will be sent to outside labs. All personal data will be protected. Samples will be destroyed when the study ends.
* Participants will get the results of genetic testing.
* Participants who cannot come to the NIH clinic may just give a cheek swab and have genetic testing done.
* Some participants will be contacted for more testing.

Background:

An estimated 1-3% of gastric cancer cases occur within a familial background as part of an inherited cancer syndrome.

Hereditary Diffuse Gastric Cancer (HDGC) is the most frequent form of familial gastric cancer and has been linked to a germline mutation in the CDH1 gene.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a more recently described autosomal dominant syndrome characterized by fundic gland polyposis with antral sparing.

Other germline mutations that predispose to gastric cancer such as SDH (succinate dehydrogenase protein subunits) gene and CTNNA1 (alpha catenin).

Objectives:

Characterize the natural and clinical histories of hereditary gastric cancer syndromes.

Eligibility:

Individuals, and family members, who fulfill clinical criteria for a hereditary gastric cancer syndrome irrespective of previous genetic testing or treatment.

Design:

These rare families will be recruited to genetically confirm diagnosis and study the natural history of hereditary gastric cancers.

Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.

We will determine if there is a relationship between mutation and disease phenotype.

Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

Characterization of the natural and clinical histories of hereditary gastric cancer syndromes

Study title	NCT ID	Conditions	Eligibility	Organization
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	NCT04431024	Familial Cancer BRCA1-Associate... Tumor Predispos... Mesothelioma	30 Years -	National Institutes of Health Clinical Center (CC)
Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer	NCT03030404	Stomach Neoplas... Stomach Cancer Gastric Adenoca... Hereditary Diff... Familial Diffus...	2 Years -	National Institutes of Health Clinical Center (CC)
Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer	NCT03030404	Stomach Neoplas... Stomach Cancer Gastric Adenoca... Hereditary Diff... Familial Diffus...	2 Years -	National Institutes of Health Clinical Center (CC)
Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer	NCT03030404	Stomach Neoplas... Stomach Cancer Gastric Adenoca... Hereditary Diff... Familial Diffus...	2 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for familial background