Familial pleura mesothelioma with environmental asbestos exposure: losses of DNA sequences by comparative genomic hybridization

Familial clustering of malignant mesothelioma (MM) is well-documented. In most families, mesothelioma develops among related individuals, in association with asbestos exposure due to work or the domestic environment. More rarely, tumours have been diagnosed in related patients without evidence of asbestos exposure, indicating that the predisposition to MM might be expressed through different oncogenic pathways. To date, only two familial clusters have been genetically studied. Here, we report on two cases of pleural MM affecting two young sisters (23 and 32 years old) of a ninemember family, who were environmentally exposed to asbestos. We performed comparative genomic hybridization (CGH) on paraffin-embedded samples following a conventional technique. CGH analysis showed largely concordant cytogenetic aberrations in both cases. Gains, including amplificatons, were more frequent than losses in both cases. In our study, CGH analysis allowed the identification of critical chromosome regions possibly involved in the pathogenesis of the MM. Our results support the hypothesis of a possible genetic component in the pathogenesis of MM and provide evidence for a recessive mechanism in the oncogenesis of this tumour.