An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation.

Abstract

We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family. 

• Authors: Mitchell Cheung, Yuwaraj Kadariya, Jianming Pei, Jacqueline Talarchek, Francesco Facciolo, Paolo Visca, Luisella Righi, Ilaria Cozzi, Joseph R Testa, Valeria Ascoli
• Journal: Cancer genetics (Cancer Genet) Vol. 208 Issue 10 Pg. 502-7 (Oct 2015) ISSN: 2210-7762 [Print] United States
• PMID: 26364129 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• BAP1 protein, human
• Tumor Suppressor Proteins
• Asbestos
• Ubiquitin Thiolesterase

Topics

• Adult
• Aged
• Aged, 80 and over
• Asbestos (adverse effects)
• Female
• Genetic Predisposition to Disease
• Humans
• Lung Neoplasms (chemically induced, genetics)
• Male
• Mesothelioma (chemically induced, genetics)
• Mesothelioma, Malignant
• Middle Aged
• Mutation
• Oligonucleotide Array Sequence Analysis
• Pedigree
• Pleural Neoplasms (chemically induced, genetics)
• Tumor Suppressor Proteins (genetics)
• Ubiquitin Thiolesterase (genetics)