BAP1 gene

Associated Syndrome Name: BAP1-Tumor Predisposition Syndrome (BAP1-TPDS)

BAP1 Summary Cancer Risk Table

Cancer Genetic Cancer Risk
OtherHigh Risk
RenalHigh Risk
SkinHigh Risk

BAP1 gene Overview

BAP1-Tumor Predisposition Syndrome (BAP1-TPDS) 1, 2, 3, 4
  • Individuals with BAP1 mutations have BAP1-Tumor Predisposition Syndrome (BAP1-TPDS).
  • The most common cancer diagnosed in individuals with BAP1-TPDS is melanoma of the eye (uveal melanoma). There is also a high risk for melanomas of the skin (cutaneous melanoma).
  • The risk for basal cell skin cancer is increased in individuals with BAP1 mutations. Although basal cell skin cancer is common in the general population, individuals with BAP1-TPDS are more likely to be diagnosed at younger ages, and with multiple tumors.
  • Individuals with BAP1-TPDS have a high risk for malignant mesothelioma, a cancer that occurs in the lungs, abdomen, or skin. Asbestos exposure is a well-known environmental risk factor for mesothelioma and it is believed that individuals with BAP1-TPDS may be especially susceptible to asbestos exposure.
  • Individuals with BAP1-TPDS have a high risk for clear cell renal cell carcinoma, a type of kidney cancer.
  • Cancers in individuals with BAP1-TPDS often develop at relatively young ages and individuals may develop more than one type of cancer.
  • Estimates of the risks for different types of cancer in individuals with BAP1-TPDS are listed in the Cancer Risk Table, but these estimates are based on small numbers of cases and are likely to change as we learn more about this condition.
  • Benign skin tumors known as BAP1-inactivated melanocytic tumors (BIMT) are likely to be the first sign of BAP1-TPDS in most patients. These are not cancers, but may have the potential to become melanomas.
  • Studies have suggested that BAP1-TPDS could also include an increased risk for a wide variety of other cancers, including hepatocellular carcinoma, cholangiocarcinoma, meningioma, breast, thyroid, lung, and others. However, more studies are needed to determine exactly which cancers are more common in people with BAP1 mutations.
  • Although there are high cancer risks for patients with BAP1-TPDS, there may be interventions that can reduce these risks. Guidelines for kidney-specific screening from the National Comprehensive Cancer Network (NCCN) for the medical management of patients with BAP1-TPDS are listed below. There are currently no professional society medical management recommendations for patients with BAP1-TPDS for the additional cancers, but suggestions from experts who study the condition are provided below. Since BAP1-TPDS is a complex condition with risks for multiple types of cancer, and evolving recommendations for screening, patients with a BAP1 mutation should be managed by a multidisciplinary team with expertise in medical genetics and the care of patients with hereditary cancer syndromes.

BAP1 gene Cancer Risk Table

Cancer Type Age Range Cancer Risk Risk for General Population
Uveal MelanomaPercentage of mutation carriers affected1, 2, 3, 4, 525%-36%<0.1% to age 80
Malignant MesotheliomaPercentage of mutation carriers affected1, 2, 3, 4, 520%-25%0.03% to age 80
Cutaneous MelanomaPercentage of mutation carriers affected1, 2, 3, 4, 513%-17%1.6% to age 80
RenalPercentage of mutation carriers affected1, 3, 4, 55%-10%1.3% to age 80
Basal Cell Skin CancerPercentage of mutation carriers affected1, 3, 4, 5, 66%-10%20% to age 70
Other - Non-malignant features of BAP1-TPDSAll ages2, 4BAP1-TPDS is associated with benign skin tumors known as BIMTs (see Overview)NA

BAP1 Cancer Risk Management Table

The overview of medical management options provided is a summary of professional society guidelines. The most recent version of each guideline should be consulted for more detailed and up-to-date information before developing a treatment plan for a particular patient.

This overview is provided for informational purposes only and does not constitute a recommendation. While the medical society guidelines summarized herein provide important and useful information, medical management decisions for any particular patient should be made in consultation between that patient and his or her healthcare provider and may differ from society guidelines based on a complete understanding of the patient’s personal medical history, surgeries and other treatments.

Cancer Type Procedure Age to Begin Frequency
(Unless otherwise indicated by findings)
Uveal MelanomaCurrently there are no specific medical management guidelines for uveal melanoma risk in mutation carriers. However, expert groups have suggested consideration of screening including eye examinations and imaging by an ocular oncologist. It may also be desirable to avoid risk factors for uveal melanoma, such as arc welding and exposure to sunlight without UV protective sunglasses.2, 3, 711 yearsAnnually
Malignant MesotheliomaCurrently there are no specific medical management guidelines for malignant mesothelioma risk in mutation carriers. However, expert groups have suggested consideration of individualized monitoring for symptoms of malignant mesothelioma, and/or Consideration of abdominal MRI or CT imaging.2, 730 yearsNA
Cutaneous MelanomaCurrently there are no specific medical management recommendations for skin melanoma risk in mutation carriers. However, the increased risk for melanoma warrants consideration of risk-reduction strategies, including frequent self-examination of the skin, consideration of clinical skin examinations, and minimizing exposure to the sun and other sources of UV radiation.2, 3, 6, 7, 818 yearsAnnually
RenalConsider abdominal MRI (preferred) or CT, with and without IV contrast.930 yearsEvery 2 years
Basal Cell Skin CancerCurrently there are no specific medical management recommendations for basal cell skin cancer risk in mutation carriers. However, the increased risk for melanoma warrants consideration of risk-reduction strategies, including frequent self-examination of the skin, consideration of clinical skin examinations, and minimizing exposure to the sun and other sources of UV radiation.2, 3, 6, 7, 818 yearsAnnually
Other - Non-malignant features of BAP1-TPDSCurrently there are no specific medical management guidelines for BIMTs in mutation carriers. However, expert groups have suggested it may be appropriate for these tumors to be monitored by a dermatologist along with monitoring for melanoma and basal cell cancer.2, 3, 718 yearsAnnually

Information for Family Members

The following information for Family Members will appear as part of the MMT for a patient found to have a mutation in the BAP1 gene.

This patient's relatives are at risk for carrying the same mutation(s) and associated cancer risks as this patient. Cancer risks for females and males who have this/these mutation(s) are provided below.

Family members should talk to a healthcare provider about genetic testing. Close relatives such as parents, children, brothers and sisters have the highest chance of having the same mutation(s) as this patient. Other more distant relatives such as cousins, aunts, uncles, and grandparents also have a chance of carrying the same mutation(s). Testing of at-risk relatives can identify those family members with the same mutation(s) who may benefit from surveillance and early intervention.

Since BAP1 mutations carry a risk for complications in children and there are some screenings that may begin in children, consideration should be given to the possibility of mutation testing in childhood.

References

  1. Haugh AM, et al. Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature. JAMA Dermatol. 2017 153:999-1006. PMID: 28793149.
  2. Pilarski R, et al. BAP1 Tumor Predisposition Syndrome. 2016 Oct 13 [updated 2020 Sep 17]. In: Adam MP, et al., editors. GeneReviews® [Internet]. PMID: 27748099.
  3. Rai K, et al. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet. 2016 89:285-94. PMID: 26096145.
  4. Walpole S, et al. Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide. J Natl Cancer Inst. 2018 110:1328-1341. PMID: 30517737.
  5. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. [Cited 2020 Sep 14]. Available from https://seer.cancer.gov/explorer/.
  6. National Council on Skin Cancer Prevention. At https://skincancerprevention.org/learning/risk-factors/what-causes-melanoma-skin-cancer/ (accessed on 08-19-2021)
  7. Star P, et al. Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy. Eur J Cancer. 2018 92:48-53. PMID: 29413689.
  8. Cancer.Net, American Society of Clinical Oncology, Melanoma: Risk Factors and Prevention 2020 Available at http://www.cancer.net/cancer-types/melanoma/risk-factors-and-prevention.
  9. Motzer RJ et al. NCCN Clinical Practice Guidelines in Oncology®: Kidney Cancer. V 1.2022. July 1. Available at https://www.nccn.org.
Last Updated on 21-Apr-2022