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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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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. |
format | Online Article Text |
id | pubmed-5580708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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