BAP1 Tumour Predisposition Syndrome
BAP1 tumour predisposition syndrome (BAP1-TPDS; ORPHA:289539, OMIM:614327) is a rare hereditary cancer syndrome characterised by an increased risk of uveal melanoma, cutaneous melanoma, malignant mesothelioma, basal cell carcinoma, and renal cell carcinoma among others. An association with meningioma, cholangiocellular carcinoma and additional tumour types has been suggested. The lifetime risk of developing a BAP1-associated tumour is estimated to be up to 85%. Individuals with BAP1-TPDS may also develop benign skin lesions called BAP1-inactivated melanocytic nevi, which can be early indicators of the syndrome. The different cancers tend to develop earlier than in the general population making early diagnosis critical for effective treatment.
BAP1 tumour predisposition syndrome is caused by heterozygous pathogenic germline variants in the BAP1 (BRCA1-associated protein 1) gene, a tumour suppressor gene. BAP1 plays a crucial role in regulating cell growth, chromatin dynamics, and maintaining genomic stability. When pathogenic variants occur in the BAP1 gene, its ability to control cell growth is impaired, leading to an increased risk of tumour development. While rare, the exact prevalence of BAP1 tumour predisposition syndrome in the general population is unknown. It is estimated to occur with a frequency of 1:26,000.
BAP1 tumour predisposition syndrome follows an autosomal dominant inheritance pattern. Although de novo occurrence of pathogenic germline variants in BAP1 has been reported, most persons with BAP1-TPDS have an affected parent. Family members may present with different tumour types associated with BAP1-TPDS. Carriers of heterozygous pathogenic variants have a 50% risk of transmitting the variant to their children. Preimplantation and prenatal genetic testing are possible when one of the parents is a carrier of a known pathogenic variant in BAP1. Family members of individuals diagnosed with BAP1 tumour predisposition syndrome should be offered genetic counselling and testing to determine their own risk.
Early tumour detection and regular monitoring are essential for individuals with BAP1 tumour predisposition syndrome (specific surveillance recommendations are given below). Surveillance strategies include dermatological exams to check for melanocytic lesions (such as BAP1-inactivated melanocytic nevi, and melanoma), annual ophthalmologic evaluations for uveal melanoma, and imaging studies like MRI or ultrasound of the kidneys. Currently, there is no established clinical surveillance method for early detection of mesothelioma, but several strategies are examined in a research setting. Depending on family history and personal risk, additional screening may be employed.
Due to the increased risk of tumours, all people with BAP1-TPDS are advised to abstain from smoking. Exposure to asbestos and additional occupational hazards (arc welding) should be avoided. Caution is advised regarding unnecessary and extensive UV exposure (e.g. through sunlight or tanning beds) and individuals with BAP1-TPDS should be educated to use sunscreen, sun glasses and protective clothing.
Surveillance recommendations
According to the “Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome” by Fiona Lalloo et al. and endorsed by ERN GENTURIS:
Recommendations for surveillance in individuals with BAP1 pathogenic variants typically include:
Skin: Annual dermatologic exams from age 18-20.
Eyes: Yearly eye exams by an ophthalmologist with expertise in uveal melanoma from age 16-18.
Abdomen/Kidneys: Imaging studies (e.g., preferably MRI or ultrasound if MRI is unavailable) yearly to monitor for kidney tumours from age 30.
Mesothelioma: Carriers should be educated about symptoms and evaluated in a specialised centre if symptomatic.
More information
For more information on BAP1 Tumour Predisposition Syndrome and surveillance options, consider visiting the following resources:
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Clinical practice guidelines |
ERN GENTURIS care pathway |
ERN GENTURIS patient journey |
ERN GENTURIS publications |
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Endorsed by ERN GENTURIS* |
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Thematic Group 4: Other rare – predominantly malignant – genturis |
* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.
ERN GENTURIS webinars - Thematic group 4: Other rare genturis
ERN GENTURIS webinars - General
A list of healthcare providers with expertise in Thematic Group 4: Other rare - predominantly malignant - genturis can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.