BAP1 Syndrome – Predisposition to Malignant Mesothelioma, Skin and Uveal Melanoma, Renal and Other Cancers

Česká verzia

Authors: Lenka Foretová ¹; Marie Navrátilová ¹; Marek Svoboda ^1,2; Jana Házová ¹; Petra Vašíčková ¹; Eva Hrabincová Sťahlová ¹; Pavel Fabian ³; Monika Schneiderová ⁴; Eva Macháčková ¹
Authors place of work: Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno ¹; Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno ²; Oddělení onkologické patologie, Masarykův onkologický ústav, Brno ³; Oddělení radiologie, Masarykův onkologický ústav, Brno ⁴
Published in the journal: Klin Onkol 2019; 32(Supplementum2): 118-122
Category: Case Report
doi: https://doi.org/10.14735/amko2019S118

Summary

Background: BAP1 syndrome is an autosomal dominant hereditary cancer syndrome associated with increased risk of malignant mesothelioma; uveal and cutaneous melanoma; kidney cancer; lung adenocarcinoma; meningioma; basaliomas; and breast, ovarian, and prostate tumors. The BAP1 gene (BRCA1-associated protein 1) is a tumor suppressor gene involved in DNA repair via homologous recombination. BAP1 regulates the cell cycle, differentiation, DNA damage responses, and cell proliferation through deubiquitination. Somatic mutations in the BAP1 gene are common in many types of tumors.

Observation: Two families harboring a germline mutation in the BAP1 gene were diagnosed at Masaryk Memorial Cancer Institute (MMCI). A 27-year-old index female from one family was followed-up for multiple nevi. Her mother and uncle had malignant mesothelioma, and her maternal grandmother had uveal melanoma. The index case tested positive for a BAP1 (NM_004656.2): c.217delG/p.Asp73Metfs*5 frame-shift mutation. The melanoma was removed at the age of 28 and 31. In the second family, an 11-year-old index female had two nevi removed from her head, and a spitzoid-type skin lesion was diagnosed at the age of 11. Her 34-year-old mother had multiple nevi, and a skin lesion of spitzoid-type was removed from the abdomen. Both patients harbored a BAP1 (NM_004656.2): c.123-1G>T acceptor splice site mutation (IARC [International Agency for Research on Cancer] class 4 [probably pathogenic]). Preventive measures for BAP1 syndrome should include known risks for cancer. Tumors occur early and repeatedly. At the MMCI, we recommend physical examination by an oncologist, eyes and skin examination, every 6 months; whole-body magnetic resonance imaging, including the central nervous system, every year (or low-dose computed tomography/chest and abdomen magnetic resonance imaging); annual abdominal ultrasound, breast ultrasound, or mammography; a gynecological ultrasound examination every 6 months; colonoscopy starting at the age of 45; and other suitable surveillances based on family history.

Conclusion: BAP1 syndrome is a complex cancer syndrome with a high risk of rare malignant mesothelioma, malignant skin and uveal melanoma, spitzoid-type skin lesions, and other tumors. Detection of this syndrome is essential for the survival of high-risk individuals.

Supported by the grant project MH CZ – RVO (MMCI, 00209805).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted: 21. 5. 2019

Accepted: 6. 6. 2019

Keywords:

genetic testing – melanoma – genes – mesothelioma – kidney neoplasms

Zdroje

1. Testa JR, Cheung M, Pei J et al. BAP1 mutations predispose to malignant mesothelioma. Nat Genet 2011; 43 (10): 1022–1025. doi: 10.1038/ng.912.

2. Testa JR, Malkin D, Schiffman JD. Connecting molecular pathways to hereditary cancer risk syndromes. Am Soc Clin Oncol Educ Book 2013: 81–90. doi: 10.1200/EdBook_AM.2013.33.81.

3. Harbour JW, Onken MD, Roberson ED et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 2010; 330 (6009): 1410–1413. doi: 10.1126/science.1194472.

4. Masoomian B, Shields JA, Shields CL. Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. J Curr Ophthalmol 2018; 30 (2): 102–109. doi: 10.1016/j.joco.2018.02.005.

5. Kittaneh M, Berkelhammer CH. Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: benefit to patient and family members. J Transl Med 2018; 16 (1): 194–201. doi: 10.1186/s12967-018-1559-7.

6. Abdel-Rahman MH, Pilarski R, Cebulla CM et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningeoma, and other cancers. J Med Genet 2011; 48 (12): 856–859. doi: 10.1136/jmedgenet-2011-100156.

7. Ghosh K, Modi B, James WD et al. BAP1: case report and insight into a novel tumor suppressor. BMC Dermatol 2017; 17 (1): 13–16. doi: 10.1186/s12895-017-0065-6.

8. Pilarski R, Cebulla CM, Massengill JB et al. Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. Genes Chromosomes Cancer 2014; 53 (2): 177–182. doi: 10.1002/gcc.22129.

9. Lin M, Zhang L, Hildebrandt MA, Huang M et al. Common, germline genetic variations in the novel tumor suppressor BAP1 and risk of developing different types of cancer. Oncotarget 2017; 8 (43): 74936–74946. doi: 10.18632/oncotarget.20465.

10. Popova T, Hebert L, Jacquemin V et al. Germline BAP1 mutations predispose to renal cell carcinomas. Am J Hum Genet 2013; 92 (6): 974–980. doi: 10.1016/j.ajhg.2013.04.012.

11. Ohar JA, Cheung M, Talarchek J et al. Germline BAP1 mutational landscape of asbestos-exposed malignant mesothelioma patiens with family history of cancer. Cancer Res 2016; 76 (2): 206–215. doi: 10.1158/0008-5472.CAN-15-0295.

12. Jensen DE, Proctor M, Marquis ST et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 1998; 16 (9): 1097–1112.

13. Bajčiová V. Maligní melanom u dětí a adolescentů. Onkologie 2013; 7 (2): 69–73.

14. Carbone M, Ferris LK, Baumann F et al. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. J Transl Med 2012; 10: 179–186. doi: 10.1186/1479-5876-10-179.

15. Carbone M, Yang H, Pass HI et al. BAP1 and cancer. Nat Rev Cancer 2013; 13 (3): 153–159. doi: 10.1038/nrc3459.

16. Star P, Goodwin A, Kapoor R et al. Germline BAP1-positive patients: the dilemmas of cancer surveillance and a proposed interdisciplinary consensus monitoring strategy. Eur J Cancer 2018; 92: 48–53. doi: 10.1016/j.ejca.2017.12.022.

17. Rai K, Pilarski R, Cebulla CM et al. Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet 2016; 89 (3): 285–294. doi: 10.1111/cge.12630.

18. Carbone M, Kanodia S, Chao A et al. Consensus report of the 2015 Weinman International Conference on mesothelioma. J Thorac Oncol 2016; 11 (8): 1246–1262. doi: 10.1016/j.jtho.2016.04.028.

19. Walpole S, Pritchard AL, Cebulla CM et al. Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. J Natl Cancer Inst 2018; 110 (2): 1328–1341. doi: 10.1093/jnci/djy171.