BAP1 hereditary cancer predisposition syndrome: a case report and review of literature

Our plain-English summary of BAP1 hereditary cancer predisposition syndrome: a case report and review of literature, by S. Klebe, J. Driml, M. Nasu, et al (Biomarker Research, 2015).

The study

• Authors: S. Klebe, J. Driml, M. Nasu, S. Pastorino, A. Zangiabadi, D. Henderson, M. Carbone
• Journal: Biomarker Research
• Published: 2015;3:14
• Type of article: Case report
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A 72-year-old woman was diagnosed with uveal melanoma, peritoneal mesothelioma and a primary biliary tract adenocarcinoma. She had a strong family history of mesothelioma as well as other malignancies including renal cell carcinoma. The recently described BAP1 hereditary cancer predisposition syndrome was suspected, but immunohistochemical labeling was not conclusive. Genetic testing confirmed a novel and unusual germline mutation in the ubiquitin hydrolase domain of the BAP1 gene (p.Tyr173Cys) and the patient was diagnosed with the BAP1 hereditary cancer predisposition syndrome. This case demonstrates the importance of clinically recognizing this rare syndrome and its manifestations, some which are still being characterized. It also highlights the importance of genetic testing in cases where there is a high clinical suspicion, even when screening tests, such as immunohistochemistry, in this case, are inconclusive. The diagnosis of a germline BAP1 mutation may have important implications for both the patient and their families with regards to further genetic testing and active surveillance programs. Further research is needed to fully understand the extent and clinical implications of this rare cancer syndrome.

In plain English

This article is a case report with a review of published literature on BAP1 hereditary cancer predisposition syndrome, an inherited condition linked to several cancers. The authors described a 72-year-old woman, reported as the first case in Australia, who was diagnosed with uveal melanoma of the left eye, epithelial-type malignant peritoneal mesothelioma, and an adenocarcinoma considered likely to be a primary intrahepatic cholangiocarcinoma (bile duct cancer). Her father and brother had both died of malignant mesothelioma after occupational asbestos exposure. She had no occupational exposure but may have had household exposure since the 1970s. Two of her four children had died, of renal cell carcinoma at age 41 and acute lymphocytic leukaemia at age 17. Tissue staining for BAP1 was inconclusive: nuclear staining was lost in the bile duct tumour but retained in the mesothelioma. Blood DNA testing found a germline BAP1 mutation (p.Tyr173Cys). She died 31 months after the cholangiocarcinoma and mesothelioma diagnoses. Tumour samples were not sequenced. The authors concluded that this was the first Australian family described with the syndrome and that the syndrome is not restricted to the US and Europe.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of one patient, followed by a review of published literature on the BAP1 cancer syndrome
• Who was studied: One 72-year-old woman, previously well, of Greek descent, reported as the first case of the syndrome in Australia; her family history is also described
• Exposure: No occupational asbestos exposure for the patient, but possible ongoing household exposure since the 1970s. Her father and brother had occupational asbestos exposure. No fiber type is stated. The main exposure of interest is a germline BAP1 mutation.
• Main results:
  • The patient was found to have uveal melanoma of the left eye
  • A liver biopsy showed poorly differentiated adenocarcinoma, considered likely to be a primary intrahepatic cholangiocarcinoma
  • A peritoneal biopsy showed malignant mesothelioma of epithelial type
  • BAP1 immunohistochemistry showed loss of nuclear labeling in the biliary tract adenocarcinoma, but nuclear labeling was retained in the mesothelioma
  • Germline DNA sequencing found a missense mutation in the BAP1 gene (g.52441252A > G, p.Tyr173Cys) in exon 7
  • The patient's father and brother had both died of malignant mesothelioma after occupational asbestos exposure
  • Two of the patient's four children had died, of renal cell carcinoma at age 41 and acute lymphocytic leukaemia at age 17
  • The patient died 31 months after diagnosis of cholangiocarcinoma and mesothelioma, from progression of her intra-abdominal cancers
• The authors' conclusion: The authors concluded that this was the first Australian family described with the BAP1 cancer syndrome, that the syndrome is not restricted to the US and Europe, and that identifying such patients is critical for medical advice and genetic counseling
• Limitations the authors state:
  • Definitive sequencing was not performed on tumour samples, because they were largely used up by diagnostic tests
  • The role of this specific mutation is not yet known

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Peritoneal Mesothelioma, Adenocarcinoma, Mesothelioma, Carcinoma, Germline Mutation, Immunohistochemistry, BAP1 Tumor Predisposition Syndrome.

Related studies

• Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases — R. Pilarski, C.M. Cebulla, et al. (2014)
• Connecting molecular pathways to hereditary cancer risk syndromes — J.R. Testa, D. Malkin, et al. (2013)
• Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist — L.M. Martorano, R.R. Winkelmann, et al. (2014)
• Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases — K. Rai, R. Pilarski, et al. (2016)
• Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma — B. Masoomian, J.A. Shields, et al. (2018)
• Families with BAP1-Tumor Predisposition Syndrome in The Netherlands: Path to Identification and a Proposal for Genetic Screening Guidelines — C. Chau, R. van Doorn, et al. (2019)

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