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

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...

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Autores principales: Huang, Mi Ni, Yu, Willie, Teoh, Wei Wei, Ardin, Maude, Jusakul, Apinya, Ng, Alvin Wei Tian, Boot, Arnoud, Abedi-Ardekani, Behnoush, Villar, Stephanie, Myint, Swe Swe, Othman, Rashidah, Poon, Song Ling, Heguy, Adriana, Olivier, Magali, Hollstein, Monica, Tan, Patrick, Teh, Bin Tean, Sabapathy, Kanaga, Zavadil, Jiri, Rozen, Steven G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580708/
https://www.ncbi.nlm.nih.gov/pubmed/28739859
http://dx.doi.org/10.1101/gr.220038.116
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author Huang, Mi Ni
Yu, Willie
Teoh, Wei Wei
Ardin, Maude
Jusakul, Apinya
Ng, Alvin Wei Tian
Boot, Arnoud
Abedi-Ardekani, Behnoush
Villar, Stephanie
Myint, Swe Swe
Othman, Rashidah
Poon, Song Ling
Heguy, Adriana
Olivier, Magali
Hollstein, Monica
Tan, Patrick
Teh, Bin Tean
Sabapathy, Kanaga
Zavadil, Jiri
Rozen, Steven G.
author_facet Huang, Mi Ni
Yu, Willie
Teoh, Wei Wei
Ardin, Maude
Jusakul, Apinya
Ng, Alvin Wei Tian
Boot, Arnoud
Abedi-Ardekani, Behnoush
Villar, Stephanie
Myint, Swe Swe
Othman, Rashidah
Poon, Song Ling
Heguy, Adriana
Olivier, Magali
Hollstein, Monica
Tan, Patrick
Teh, Bin Tean
Sabapathy, Kanaga
Zavadil, Jiri
Rozen, Steven G.
author_sort Huang, Mi Ni
collection PubMed
description 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.
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spelling pubmed-55807082017-09-14 Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors Huang, Mi Ni Yu, Willie Teoh, Wei Wei Ardin, Maude Jusakul, Apinya Ng, Alvin Wei Tian Boot, Arnoud Abedi-Ardekani, Behnoush Villar, Stephanie Myint, Swe Swe Othman, Rashidah Poon, Song Ling Heguy, Adriana Olivier, Magali Hollstein, Monica Tan, Patrick Teh, Bin Tean Sabapathy, Kanaga Zavadil, Jiri Rozen, Steven G. Genome Res Research 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. Cold Spring Harbor Laboratory Press 2017-09 /pmc/articles/PMC5580708/ /pubmed/28739859 http://dx.doi.org/10.1101/gr.220038.116 Text en © 2017 Huang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Huang, Mi Ni
Yu, Willie
Teoh, Wei Wei
Ardin, Maude
Jusakul, Apinya
Ng, Alvin Wei Tian
Boot, Arnoud
Abedi-Ardekani, Behnoush
Villar, Stephanie
Myint, Swe Swe
Othman, Rashidah
Poon, Song Ling
Heguy, Adriana
Olivier, Magali
Hollstein, Monica
Tan, Patrick
Teh, Bin Tean
Sabapathy, Kanaga
Zavadil, Jiri
Rozen, Steven G.
Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title_full Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title_fullStr Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title_full_unstemmed Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title_short Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
title_sort genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580708/
https://www.ncbi.nlm.nih.gov/pubmed/28739859
http://dx.doi.org/10.1101/gr.220038.116
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