Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma

Abstract

Familial clustering of malignant mesothelioma (MM) has been linked to the presence of germline mutations in BAP1. However, families with multiple MM patients, without segregating BAP1 mutation were described, suggesting the existence of other predisposing genetic factors. In this study, we report a previously undescribed Belgian family, in which BAP1 was found to be absent in the epithelial malignant mesothelial cells of the index patient. Whole exome analysis did not reveal a germline or somatic BAP1 variant. Also, no germline or somatic copy number changes in the BAP1 region could be identified. However, germline variants, predicted to be damaging, were detected in 11 other ‘Cancer census genes’ (i.e. MPL, RBM15, TET2, FAT1, HLA-A, EGFR, KMT2C, BRD3, NOTCH1, RB1 and MYO5A). Of these, the one in RBM15 seems to be the most interesting given its low minor allele frequency and absence in the germline DNA of the index patient’s mother. The importance of this ‘Cancer census gene’ in familial MM clustering needs to be evaluated further. Nevertheless, this study strengthens the suspicion that, next to germline BAP1 alterations, other genetic factors might predispose families to the development of MM.

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Acknowledgements

The human biological material of the index patient was provided by Biobank@UZA (Antwerp University Hospital, Belgium; ID: BE71030031000, funded by the Belgian National Cancer Plan). We also want to thank Sisca Kohl, nursing counselor at the Thoracic Oncology department of the Antwerp University Hospital, for helping with the collection of the peripheral blood samples of the family members.

Funding

This work was realized with an Emmanuel van der Schueren research grant from the Flemish League against Cancer and grant 2016/818 from the Belgian Foundation against Cancer.

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Correspondence to Jan P. van Meerbeeck.

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Hylebos, M., Op de Beeck, K., van den Ende, J. et al. Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma. Familial Cancer 17, 569–576 (2018). https://doi.org/10.1007/s10689-018-0095-1

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Keywords

  • Malignant mesothelioma
  • Familial cancer
  • Cancer predisposition
  • BAP1
  • Cancer census genes