John M. Essigmann, Ph.D.
Massachusetts Institute of Technology
R01ES016313, T32ES007020, P30ES002109
NIEHS grantees developed a way to determine whether liver cells have been exposed to aflatoxin B1 (AFB1), a fungal product that is a known liver carcinogen. Their new powerful DNA sequencing technique has the potential to identify mutations associated with AFB1 exposure long before cancer develops.
Mice exposed to aflatoxin 4 days after birth eventually developed liver cancer. The researchers sequenced DNA from the mice tumors and from liver cells before the tumors developed. Using a new genome sequencing technique, they identified patterns in DNA mutations associated with the AFB1 exposure. These mutation patterns emerged as soon as 10 weeks after exposure, before any signs of tumors.
The researchers compared the mutational profile of the aflatoxin-exposed mice to genetic sequences found in liver tumors in patients from around the world. They found that the signature of the mouse cells closely matched the signatures of 13 patients believed to have been exposed to aflatoxin through their diet.
According to the authors, this technique has promise for predicting whether someone exposed to AFB1 has a high risk of developing liver cancer, providing a potential opportunity for early detection and management.
Citation: Chawanthayatham S, Valentine CC 3rd, Fedeles BI, Fox EJ, Loebd LA, Levine SS, Slocum SL, Wogan GN, Croy RG, Essigmann JM. 2017. Mutational spectra of aflatoxin B1 in vivo establish biomarkers of exposure for human hepatocellular carcinoma. Proc Natl Acad Sci U S A 114(15):E3101–E3109.