NTP mines tissue archives for liver cancer mutations
To understand the mechanisms of carcinogenesis, scientists from the National Toxicology Program (NTP) used exome sequencing to examine mouse hepatocellular carcinomas (HCCs) that arose spontaneously or were due to long-term chemical exposures. Using this genomic technique, the team sequenced all of the protein-coding genes to document the genetic mutations present in HCC samples that were derived from archival tissues from NTP rodent cancer bioassays. In humans, HCCs are the third leading cause of cancer-related deaths worldwide.
The archival tumor samples were derived from previous 2-year NTP rodent cancer bioassays with ginkgo biloba extract, a common herbal supplement, and methyleugenol, a food-flavoring agent. In both studies, B6C3F1/N mice developed HCCs in a dose-dependent manner. The samples were either flash frozen or fixed in formalin and embedded in paraffin. The scientists found that by using exome sequencing, they could identify tumor or chemical-specific mutational signatures and key cancer genes. This information could help establish potential biomarkers and enhance overall understanding of carcinogenesis. The team recommended that the study be expanded to include more samples and a greater variety of chemical compounds. (EH)
Citation: Auerbach SS, Xu M, Merrick BA, Hoenerhoff MJ, Phadke D, Taxman DJ, Shah R, Hong HL, Ton TV, Kovi RC, Sills RC, Pandiri AR 2018. Exome sequencing of fresh-frozen or formalin-fixed paraffin-embedded B6C3F1/N mouse hepatocellular carcinomas arising either spontaneously or due to chronic chemical exposure. Toxicol Pathol; doi: 10.1177/0192623318789398 [Online 25 July 2018].