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

Publication ,  Journal Article
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 ...
Published in: Genome Res
September 2017

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.

Duke Scholars

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

September 2017

Volume

27

Issue

9

Start / End Page

1475 / 1486

Location

United States

Related Subject Headings

  • Mutation
  • Mice
  • Liver Neoplasms
  • Humans
  • Hepatitis B Surface Antigens
  • DNA Mutational Analysis
  • China
  • Cell Line, Tumor
  • Carcinoma, Hepatocellular
  • Carcinogens
 

Citation

APA
Chicago
ICMJE
MLA
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Huang, M. N., Yu, W., Teoh, W. W., Ardin, M., Jusakul, A., Ng, A. W. T., … Rozen, S. G. (2017). Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors. Genome Res, 27(9), 1475–1486. https://doi.org/10.1101/gr.220038.116
Huang, Mi Ni, Willie Yu, Wei Wei Teoh, Maude Ardin, Apinya Jusakul, Alvin Wei Tian Ng, Arnoud Boot, et al. “Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.Genome Res 27, no. 9 (September 2017): 1475–86. https://doi.org/10.1101/gr.220038.116.
Huang MN, Yu W, Teoh WW, Ardin M, Jusakul A, Ng AWT, et al. Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors. Genome Res. 2017 Sep;27(9):1475–86.
Huang, Mi Ni, et al. “Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.Genome Res, vol. 27, no. 9, Sept. 2017, pp. 1475–86. Pubmed, doi:10.1101/gr.220038.116.
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. Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors. Genome Res. 2017 Sep;27(9):1475–1486.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

September 2017

Volume

27

Issue

9

Start / End Page

1475 / 1486

Location

United States

Related Subject Headings

  • Mutation
  • Mice
  • Liver Neoplasms
  • Humans
  • Hepatitis B Surface Antigens
  • DNA Mutational Analysis
  • China
  • Cell Line, Tumor
  • Carcinoma, Hepatocellular
  • Carcinogens