Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome

• Published in: European journal of human genetics : EJHG 2023-11, Vol.31 (11), p.1261-1269
• Main Authors: Lalloo, Fiona, Kulkarni, Anju, Chau, Cindy, Nielsen, Maartje, Sheaff, Michael, Steele, Jeremy, van Doorn, Remco, Wadt, Karin, Hamill, Monica, Torr, Beth, Tischkowitz, Marc, Hanson, Helen
• Format: Article
• Language: English
• Subjects: BRCA1 protein; Clinical practice guidelines; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Kidney Neoplasms - genetics; Literature reviews; Medicin och hälsovetenskap; Melanoma; Melanoma - genetics; Mesothelioma; Mesothelioma - diagnosis; Mesothelioma - genetics; Neoplastic Syndromes, Hereditary - diagnosis; Neoplastic Syndromes, Hereditary - genetics; Phenotypes; Renal cell carcinoma; Surveillance; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumors; Ubiquitin Thiolesterase - genetics
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/s41431-023-01448-z

BRCA1-associated protein-1 (BAP1) is a recognised tumour suppressor gene. Germline BAP1 pathogenic/likely pathogenic variants are associated with predisposition to multiple tumours, including uveal melanoma, malignant pleural and peritoneal mesothelioma, renal cell carcinoma and specific non-malignant neoplasms of the skin, as part of the autosomal dominant BAP1-tumour predisposition syndrome. The overall lifetime risk for BAP1 carriers to develop at least one BAP1-associated tumour is up to 85%, although due to ascertainment bias, current estimates of risk are likely to be overestimated. As for many rare cancer predisposition syndromes, there is limited scientific evidence to support the utility of surveillance and, therefore, management recommendations for BAP1 carriers are based on expert opinion. To date, European recommendations for BAP1 carriers have not been published but are necessary due to the emerging phenotype of this recently described syndrome and increased identification of BAP1 carriers via large gene panels or tumour sequencing. To address this, the Clinical Guideline Working Group of the CanGene-CanVar project in the United Kingdom invited European collaborators to collaborate to develop guidelines to harmonize surveillance programmes within Europe. Recommendations with respect to BAP1 testing and surveillance were achieved following literature review and Delphi survey completed by a core group and an extended expert group of 34 European specialists including Geneticists, Ophthalmologists, Oncologists, Dermatologists and Pathologists. It is recognised that these largely evidence-based but pragmatic recommendations will evolve over time as further data from research collaborations informs the phenotypic spectrum and surveillance outcomes.