BAP1 germline variants in Finnish patients with malignant mesothelioma

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Repo , P , Staskiewicz , A , Sutinen , E , Rönty , M , Kivelä , T T , Myllärniemi , M & Turunen , J A 2022 , ' BAP1 germline variants in Finnish patients with malignant mesothelioma ' , Lung Cancer , vol. 165 , pp. 102-107 .

Title: BAP1 germline variants in Finnish patients with malignant mesothelioma
Author: Repo, Pauliina; Staskiewicz, Aleksandra; Sutinen, Eva; Rönty, Mikko; Kivelä, Tero T.; Myllärniemi, Marjukka; Turunen, Joni A.
Contributor organization: Silmäklinikka
HUS Head and Neck Center
HUS Heart and Lung Center
Department of Medicine
University of Helsinki
Keuhkosairauksien yksikkö
INDIVIDRUG - Individualized Drug Therapy
Department of Pathology
HUS Diagnostic Center
Department of Ophthalmology and Otorhinolaryngology
Date: 2022-03
Language: eng
Number of pages: 6
Belongs to series: Lung Cancer
ISSN: 0169-5002
Abstract: Objectives: Although asbestos exposure is the most common cause of malignant mesothelioma (MM), an aggressive cancer of the pleura or peritoneum, up to 7% of patients harbor a genetic predisposition to MM. Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause a dominantly inherited tumor predisposition syndrome, BAP1-TPDS, in which MM is the second most common associated cancer. Other frequent cancers in BAP1-TPDS are uveal melanoma (UM), cutaneous melanoma and renal cell carcinoma. Additionally patients can exhibit benign skin lesions, BAP1-inactivated nevi (BIN). Most BINs arise sporadically, but patients with BAP1-TPDS may harbor multiple BINs before other tumors or as the only indication of the syndrome. Our objective was to establish the frequency of pathogenic germline BAP1 variants in Finnish patients with MM. Materials and methods: 56 DNA samples archived in the Helsinki Biobank from Finnish patients with MM were sequenced for germline BAP1 variations. Formalin fixed paraffin embedded nevi from a pathogenic variant carrier were subjected to immunohistochemistry and exome sequencing. Results: Sanger sequencing identified one patient with Finnish founder mutation c.1780_1781insT, p. (G549Vfs*49) in BAP1. The carrier was diagnosed with MM over fifteen years before the cohorts mean onset age (mean 68, range 27 to 82) although the patient had no asbestos exposure or family history of BAP1-TPDS. However, the patient had three BINs removed prior to the MM. The c.1780_1781insT is now found from five Finnish BAP1-TPDS families with unknown common ancestor. Conclusion: The frequency of pathogenic germline BAP1 variants in Finnish patients with MM is 1.8 % (95 % CI, 0.04 to 9.2), comparable to the frequency in Finnish patients with UM (1.9 %). The frequency of recurring BINs in patients with BAP1-TPDS should be studied further and genetic testing for BAP1 variants considered if the patient has >= 2 BAP1-TPDS core tumors, including BINs.
Subject: Malignant mesothelioma
Tumor predisposition
BAP1-inactivated nevus
3122 Cancers
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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