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

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  • Fiona Lalloo
  • Anju Kulkarni
  • Cindy Chau
  • Maartje Nielsen
  • Michael Sheaff
  • Jeremy Steele
  • Remco van Doorn
  • Monica Hamill
  • Beth Torr
  • Marc Tischkowitz
  • Munaza Ahmed
  • Svetlana Bajalica-Lagercrantz
  • Ana Blatnik
  • Joan Brunet
  • Ruth Cleaver
  • Chrystelle Colas
  • Tabib Dabir
  • D. Gareth Evans
  • Shirin Feshtali
  • Paola Ghiorzo
  • Lise Graversen
  • Klaus Griewank
  • Hildur Helgadottir
  • Rosalyn Jewell
  • Kelly Kohut
  • Henrik Lorentzen
  • Daniela Massi
  • Guy Missotten
  • Alex Murray
  • Jennie Murray
  • Ernest Nadal
  • Kai Ren Ong
  • Josep M. Piulats
  • Susana Puig
  • Neil Rajan
  • Simone Ribero
  • Galateau Salle
  • Alexandre Teulé
  • Emma Tham
  • Barbara van Paassen
  • Robin De Putter
  • Robert Verdijk
  • Anja Wagner
  • Emma R. Woodward
  • Helen Hanson

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.

Original languageEnglish
JournalEuropean Journal of Human Genetics
Volume31
Pages (from-to)1261–1269
Number of pages9
ISSN1018-4813
DOIs
Publication statusPublished - 2023

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