MicheleCarboneMD

Summary

• I proposed that genetics influenced asbestos carcinogenesis, studied this hypothesis in remote areas of the world and designed the experiments that answered these questions. The success of our research is largely the result of teamwork. My team and I discovered that heterozygous germline BAP1 mutations modulate susceptibility to asbestos and UV-light and cause mesothelioma and eye-melanoma, and elucidated the mechanisms. My research is a combination of the field-work I conducted over 12 years in Cappadocia and in remote areas of the US, with molecular genetics and clinical-diagnostic work. Going against current dogma, I hypothesized and then proved that genetics caused familiar mesothelioma. My team and I discovered that heterozygous germline BAP1 mutations cause a novel cancer syndrome with ~100% penetrance and high incidence of mesothelioma, and we elucidated the mechanisms of BAP1 activity. We discovered novel mechanisms of asbestos carcinogenesis and elucidated how gene x environment (GxE) interaction among asbestos and germline BAP1 mutations modulate the incidence of mesothelioma. We built a family tree of ~80,000 and linked germline mutations to significantly improved prognosis. We discovered additional germline mutations that increase susceptibility to asbestos and mesothelioma. We implemented preventive and early detection strategies among the affected family members which are saving lives. We demonstrated that somatic biallelic BAP1 mutations are the most common genetic alteration in mesothelioma, elucidated how they form, and discovered the value of BAP1 immunostaining in diagnosis. Our findings have been confirmed by many laboratories and have been translated to the clinic: BAP1 genetic screening for prognosis and cancer prevention, and immunostaining for diagnosis are now routine worldwide. Moreover, we worked with Federal and State governments, in US and Turkey, to implement novel preventive approaches based on our discoveries that are expected to save