The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma; less frequently breast cancer, several types of skin carcinomas and other tumor types. Mesotheliomas in these patients are significantly less aggressive and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, significant medical, social and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life and is also cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges and our recommendations of how to best care for these patients and their family members, as well as the potential economic and psychosocial impact.
Carbone M, Pass HI, Ak G, Alexander Jr HR, Baas P, Baumann F, Blakely AM, Bueno R, Bzura. A, Cardillo G, Churpek JE, Dianzani I, De Rienzo A, Emi M, Emri S, Felley-Bosco E, Fennell DA, Flores RM, Grosso F, Hayward NK, Hesdorffer M, Hoang CD, Johansson PA, Kindler HL, Kittaneh M, Krausz T, Mansfield A, Metintas M, Minaai M, Mutti L, Nielsen M, O’Byrne K, Opitz I, Pastorino S, Pentimalli F, de Perrot M, Pritchard A, Ripley RT, Robinson B, Rusch V, Taioli E, Takinishi Y, Tanji M, Tsao AS, Tuncer AM, Walpole S, Wolf A, Yang H, Yoshikawa Y, Zolodnick A, Schrump DS, Hassan R,
Journal of Thoracic Oncology