Vinyl Chloride May Cause Ethenoguanine Adduct Mutation in Critical K-ras Gene Region Causing Rare Human Liver Cancer; Next-Gen Sequencing Plays Key Role in This MIT-Led Study

In the 1970s, epidemiologists found that workers in factories using vinyl chloride (image), the key ingredient for PVC plastics, had unusually high rates of a rare form of liver cancer called hepatic angiosarcoma. Biologists later identified a mutation that appears to be associated with this cancer, which originates in cells of the blood vessels that feed the liver. Now, using new sequencing technology that enables large-scale analysis of DNA-damage-associated mutations, MIT researchers have pinpointed the specific type of DNA damage that may be responsible for this mutation. With this knowledge, scientists could develop tests to monitor workers who might be exposed to vinyl chloride, because it has been previously shown that this type of DNA damage can be detected as a biomarker in urine samples. This could alert factories that they need to improve their safety practices if their workers are being exposed to too much vinyl chloride. The research also lays the groundwork for applying this technology to identify other types of DNA damage, also called DNA lesions or adducts, that may be responsible for certain types of cancers. The initiation of many cancers may arise from the mutations generated by DNA lesions that are produced by natural processes such as inflammation, or by exposure to environmental agents such as vinyl chloride. These processes generate a variety of DNA lesions, making the identification of the most significant lesion a challenging task. “I can think of a dozen different lesions this technology could be applied to,” says John Essigmann, the William R. and Betsy P. Leitch Professor of Chemistry and a Professor of Toxicology and Biological Engineering.
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