Diagnostics (Jul 2022)
Diagnostics of <i>BAP1</i>-Tumor Predisposition Syndrome by a Multitesting Approach: A Ten-Year-Long Experience
- Marika Sculco,
- Marta La Vecchia,
- Anna Aspesi,
- Michela Giulia Clavenna,
- Michela Salvo,
- Giulia Borgonovi,
- Alessandra Pittaro,
- Gianluca Witel,
- Francesca Napoli,
- Angela Listì,
- Federica Grosso,
- Roberta Libener,
- Antonio Maconi,
- Ottavio Rena,
- Renzo Boldorini,
- Daniela Giachino,
- Paolo Bironzo,
- Antonella Maffè,
- Greta Alì,
- Lisa Elefanti,
- Chiara Menin,
- Luisella Righi,
- Cristian Tampieri,
- Giorgio Vittorio Scagliotti,
- Caterina Dianzani,
- Daniela Ferrante,
- Enrica Migliore,
- Corrado Magnani,
- Dario Mirabelli,
- Giuseppe Matullo,
- Irma Dianzani
Affiliations
- Marika Sculco
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Marta La Vecchia
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Anna Aspesi
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Michela Giulia Clavenna
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Michela Salvo
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Giulia Borgonovi
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Alessandra Pittaro
- Pathology Unit, AOU Città della Salute e della Scienza, 10126 Turin, Italy
- Gianluca Witel
- Department of Medical Sciences, Università di Torino, 10126 Turin, Italy
- Francesca Napoli
- Department of Oncology, Università di Torino at San Luigi Hospital, 10043 Turin, Italy
- Angela Listì
- Department of Oncology, Università di Torino at San Luigi Hospital, 10043 Turin, Italy
- Federica Grosso
- Mesothelioma Unit, AO SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Roberta Libener
- Department of Integrated Activities Research and Innovation, AO SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Antonio Maconi
- Department of Integrated Activities Research and Innovation, AO SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Ottavio Rena
- Thoracic Surgery Unit, AOU Maggiore della Carità, 28100 Novara, Italy
- Renzo Boldorini
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Daniela Giachino
- Medical Genetics Unit, Department of Clinical and Biological Sciences, Università di Torino, AOU S. Luigi Gonzaga, 10043 Turin, Italy
- Paolo Bironzo
- Department of Oncology, Università di Torino at San Luigi Hospital, 10043 Turin, Italy
- Antonella Maffè
- Genetics and Molecular Biology Unit, Santa Croce e Carle Hospital, 12100 Cuneo, Italy
- Greta Alì
- Unit of Pathological Anatomy, University Hospital of Pisa, 56126 Pisa, Italy
- Lisa Elefanti
- Immunology and Diagnostics Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
- Chiara Menin
- Immunology and Diagnostics Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy
- Luisella Righi
- Department of Oncology, Università di Torino at San Luigi Hospital, 10043 Turin, Italy
- Cristian Tampieri
- Pathology Unit, Department of Medical Sciences, AOU Città della Salute e della Scienza, 10126 Turin, Italy
- Giorgio Vittorio Scagliotti
- Department of Oncology, Università di Torino at San Luigi Hospital, 10043 Turin, Italy
- Caterina Dianzani
- Department of Plastic, Reconstructive and Cosmetic Surgery, Campus Bio-Medico University Hospital, 00128 Rome, Italy
- Daniela Ferrante
- Unit of Medical Statistics, Department of Translational Medicine, Università del Piemonte Orientale and Cancer Epidemiology, CPO Piemonte, 28100 Novara, Italy
- Enrica Migliore
- Unit of Cancer Epidemiology, Città della Salute e della Scienza, University-Hospital and Center for Cancer Prevention (CPO), 10126 Turin, Italy
- Corrado Magnani
- Unit of Medical Statistics, Department of Translational Medicine, Università del Piemonte Orientale and Cancer Epidemiology, CPO Piemonte, 28100 Novara, Italy
- Dario Mirabelli
- Unit of Cancer Epidemiology, Città della Salute e della Scienza, University-Hospital and Center for Cancer Prevention (CPO), 10126 Turin, Italy
- Giuseppe Matullo
- Department of Medical Sciences, Università di Torino, 10126 Turin, Italy
- Irma Dianzani
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- DOI
- https://doi.org/10.3390/diagnostics12071710
- Journal volume & issue
-
Vol. 12,
no. 7
p. 1710
Abstract
Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.
Keywords