Molecular analysis of an asbestos-exposed Belgian family with a high prevalence of mesothelioma.
Fam Cancer
; 17(4): 569-576, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-29961174
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Amianto
/
Proteínas Supressoras de Tumor
/
Ubiquitina Tiolesterase
/
Neoplasias Pulmonares
/
Mesotelioma
Tipo de estudo:
Prevalence_studies
/
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Fam Cancer
Ano de publicação:
2018
Tipo de documento:
Article