BAP1-Dependent Tumor Predisposition Syndrome – Definition

BAP1-dependent tumor predisposition syndrome (OMIM; 614327) describes a cancer predisposition syndrome that can lead to a variety of malignant neoplasms. These neoplasms include uveal and malignant melanomas, malignant mesotheliomas, and renal cell carcinomas.

Synonym:

BAP1-TPDS

Gene:

BAP1 = BRCA1-associated protein-1

Gene ­product:

Repair proteins

Function:

Tumor suppressor gene

Pattern of inheritance:

Autosomal dominant

Prevalence:

Subject of current research

Genotype-phenotype correlation:

Subject of current research

Penetrance:

Subject of current research

Overview of the Chapters on This Page:

  • BAP1-Dependent Tumor Predisposition Syndrome – Definition (This Section)
  • BAP1-Dependent Tumor Predisposition Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

  • BAP1-Dependent Tumor Predisposition Syndrome – Definition (This Section)
  • BAP1-Dependent Tumor Predisposition Syndrome – Diagnosis

  • Clinical Presentation

  • Special Features of Treatment

  • Recommendations for Early Detection in Your Patients

  • Further Information (e.g., Links to Support Groups)

BAP1-Dependent Tumor Predisposition Syndrome – Diagnosis

The diagnosis is made by genetic detection of a BAP1 mutation. A genetic test for a BAP1 mutation is recommended in the case of an accumulation of BAP1-TPDS-associated tumors within the family. In addition, family members of BAP1 mutation carriers should also be recommended genetic testing due to the high risk of cancer.

Differential Diagnoses

Several other genetic mutations are associated with an increased risk of uveal or malignant melanoma, pleural mesothelioma, or renal cell carcinoma. However, no genetic mutation is known to be associated with an increased risk for the combination of all cancers as in BAP1-TPDS.
Gene mutations for the respective cancer that should be considered in the differential diagnosis:

  • Uveal melanoma:
    • BRCA2 mutation
  • Malignant melanoma:
    • CDKN2A mutation
    • CDK4 mutation
    • MC1R mutation
    • MITF mutation
  • Familial renal cell carcinoma:
    • Von Hippel-Lindau syndrome: VHL mutation
    • Translocation chromosome 3
    • Hereditary pheochromocytoma-paraganglioma syndrome:
      SDHA; SDHB; SDHC; SDHD; SDHAF2; MAX mutations

Clinical Presentation

BAP1-TPDS patients are characterized by the frequent occurrence of a large number of tumors:

Uveal melanoma is the most common cancer among BAP1-TPDS patients (diagnosed in 31% of all BAP1 mutation carriers). According to scientific studies, uveal melanoma is assumed to be more aggressive in BAP1 mutation carriers than in the rest of the population.

Malignant mesothelioma is the second most common cancer in BAP1 mutation carriers. In general, pleural mesothelioma occurs in 80% of cases, in contrast to peritoneal mesothelioma. However, the ratio of peritoneal to pleural mesothelioma is higher in BAP1 mutation carriers. In contrast to other types of cancer, such as uveal and malignant melanoma or renal cell carcinoma, numerous studies have assumed that the probability of survival could be longer in malignant mesothelioma.

Malignant melanoma occurs in 13% of BAP1-TPDS patients, making it the third most common tumor. Here, too, the mean age of onset is earlier in BAP1 mutation carriers than in the rest of the population (46 years vs. 58 years).

Renal cell carcinoma is also one of the BAP1-TPDS-associated cancers. The average age of onset for BAP1-TPDS patients is 47 years, compared to 64 years for non-mutation carriers.

Basal cell carcinoma also belongs to the tumor spectrum of the BAP1 tumor predisposition syndrome. Here, the average age of onset for mutation carriers is around 50 years.

Other cancers that probably belong to the BAP1-TPDS spectrum but have not yet been definitively proven:
Breast carcinoma, cholangiocarcinoma, meningioma, neuroendocrine tumors, non-small cell adenocarcinoma of the lung, thyroid carcinoma

Special Features of Treatment

Treatment of BAP1-TPDS is primarily symptomatic and should be carried out by a professional, multidisciplinary team.
Studies show that certain cancers are more aggressive in BAP1 mutation carriers, whereas pleural mesothelioma appears to be less aggressive than in non-mutation carriers. Accordingly, stronger therapy is recommended for more aggressive tumors. The early detection examinations listed below by experts are particularly important in detecting tumors in good time and treating them successfully.

Preventive Measures

  • Uveal melanoma:
    • Arc welding should be avoided as it is associated with an increased risk of UM
    • Sunglasses with high UVA and UVB protection could reduce the risk of cancer
  • Pleural mesothelioma:
    • Asbestos exposure and cigarette smoking should be avoided
  • Malignant melanoma:
    • Reduce exposure to sunlight
    • Wear sunscreen and protective clothing during UV exposure
    • Regular medical examination

Diagnosis BAP1-Dependent Tumor Predisposition Syndrome- What's Next?

Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.

Diagnosis of BAP1-Dependent Tumor Predisposition Syndrome- What's Next?

Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.

Recommendations for Early Detection in Your Patients

Uveal Melanoma

  • Annual eye examinations and ophthalmological imaging by an oncologist specializing in the eye → from the age of 11.
  • If a uveal melanoma has been diagnosed, the patient should be monitored more closely according to the protocol for the early detection of systemic metastasis in high-risk patients (e.g., liver imaging every 3-6 months, lung imaging every 6-12 months)

Malignant Mesothelioma

  • Annual physical examinations are recommended

Malignant Melanoma, Basal Cell Carcinoma and Atypical Tip Tumor

  • Annual dermatological full-body examination → from 20 years of age
  • Self-examination of the skin according to the ABCD scheme → Observe the characteristic features of melanoma
  • Use sun protection
  • If a typical Spitz tumor is found, genetic testing for a BRAF mutation and immunostaining of the BAP1 gene should be performed

Renal Cell Carcinoma

  • The renal screening protocol for von Hippel-Lindau (VHL) syndrome (annual abdominal ultrasound)

BAP1-Dependent Tumor Predisposition Syndrome – weitere Informationen

Open Clinical Trials/ Registries

Support Groups

Unfortunately, we are currently not aware of any support groups for patients with BAP1-TPDS. New information will be added as soon as it becomes available.