Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.

Published

Journal Article

Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data on the mutational signatures of AFB1 exposure from a total of >40,000 mutations in four experimental systems: two different human cell lines, in liver tumors in wild-type mice, and in mice that carried a hepatitis B surface antigen transgene-this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence.

Full Text

Duke Authors

Cited Authors

  • Huang, MN; Yu, W; Teoh, WW; Ardin, M; Jusakul, A; Ng, AWT; Boot, A; Abedi-Ardekani, B; Villar, S; Myint, SS; Othman, R; Poon, SL; Heguy, A; Olivier, M; Hollstein, M; Tan, P; Teh, BT; Sabapathy, K; Zavadil, J; Rozen, SG

Published Date

  • September 2017

Published In

Volume / Issue

  • 27 / 9

Start / End Page

  • 1475 - 1486

PubMed ID

  • 28739859

Pubmed Central ID

  • 28739859

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.220038.116

Language

  • eng

Conference Location

  • United States