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Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome
Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To dat...
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| Published in: | Journal of exposure science & environmental epidemiology 2015-05, Vol.25 (3), p.256-263 |
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| container_end_page | 263 |
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| container_title | Journal of exposure science & environmental epidemiology |
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| creator | Tanase, Anna-Maria Marchio, Agnès Dumitrascu, Traian Dima, Simona Herlea, Vlad Oprisan, Gabriela Dejean, Anne Popescu, Irinel Pineau, Pascal |
| description | Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (
NRF2
,
KEAP1
,
SRXN1
, and
CES1
) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for
β
-catenin and NRF2 (
P |
| doi_str_mv | 10.1038/jes.2014.16 |
| format | article |
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NRF2
,
KEAP1
,
SRXN1
, and
CES1
) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for
β
-catenin and NRF2 (
P
<0.0001). Besides, tumors from patients born in Greater Bucharest carried
TP53
mutations more frequently than others (45
vs
10%,
P
=0.02). Finally, a R249S mutation of
TP53
, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.</description><identifier>ISSN: 1559-0631</identifier><identifier>EISSN: 1559-064X</identifier><identifier>DOI: 10.1038/jes.2014.16</identifier><identifier>PMID: 24736102</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/737 ; 692/699/67/1504/1610 ; 692/699/67/2324 ; 704/172 ; Adult ; Aflatoxin B1 ; Aflatoxins ; Aged ; Analysis ; Biochemistry, Molecular Biology ; Biomarkers, Tumor - genetics ; Cancer ; Carcinoma, Hepatocellular - chemically induced ; Carcinoma, Hepatocellular - genetics ; Chemical mutagenesis ; Deoxyribonucleic acid ; DNA ; DNA, Mitochondrial - drug effects ; Environmental aspects ; Environmental Exposure - adverse effects ; Environmental factors ; Environmental Pollutants - toxicity ; Epidemiology ; Female ; Gene expression ; Gene mutations ; Genes ; Genetic aspects ; Genetic Markers ; Genomic analysis ; Genomics ; Hepatitis ; Hepatocellular carcinoma ; Hepatoma ; Human health and pathology ; Humans ; Hépatology and Gastroenterology ; Life Sciences ; Liver cancer ; Liver Neoplasms - chemically induced ; Liver Neoplasms - genetics ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Mitochondria ; Mortality ; Mutation ; NRF2 protein ; Oncology, Experimental ; original-article ; Oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - genetics ; p53 Protein ; Point Mutation - drug effects ; Pollutants ; Prospective Studies ; Risk analysis ; Risk Factors ; Romania ; Tumors ; Western Europe ; β-Catenin</subject><ispartof>Journal of exposure science & environmental epidemiology, 2015-05, Vol.25 (3), p.256-263</ispartof><rights>Nature America, Inc. 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 2015</rights><rights>Nature America, Inc. 2015.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c689t-50f7e15c7f78dd1b16cd4334ab2b6e9116931a2ae6b1ac9af3865b22d17ac9f3</citedby><cites>FETCH-LOGICAL-c689t-50f7e15c7f78dd1b16cd4334ab2b6e9116931a2ae6b1ac9af3865b22d17ac9f3</cites><orcidid>0000-0001-6541-5395 ; 0000-0002-9407-1592 ; 0000-0003-4778-6840</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24736102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-02863018$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanase, Anna-Maria</creatorcontrib><creatorcontrib>Marchio, Agnès</creatorcontrib><creatorcontrib>Dumitrascu, Traian</creatorcontrib><creatorcontrib>Dima, Simona</creatorcontrib><creatorcontrib>Herlea, Vlad</creatorcontrib><creatorcontrib>Oprisan, Gabriela</creatorcontrib><creatorcontrib>Dejean, Anne</creatorcontrib><creatorcontrib>Popescu, Irinel</creatorcontrib><creatorcontrib>Pineau, Pascal</creatorcontrib><title>Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome</title><title>Journal of exposure science & environmental epidemiology</title><addtitle>J Expo Sci Environ Epidemiol</addtitle><addtitle>J Expo Sci Environ Epidemiol</addtitle><description>Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (
NRF2
,
KEAP1
,
SRXN1
, and
CES1
) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for
β
-catenin and NRF2 (
P
<0.0001). Besides, tumors from patients born in Greater Bucharest carried
TP53
mutations more frequently than others (45
vs
10%,
P
=0.02). Finally, a R249S mutation of
TP53
, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.</description><subject>631/208/737</subject><subject>692/699/67/1504/1610</subject><subject>692/699/67/2324</subject><subject>704/172</subject><subject>Adult</subject><subject>Aflatoxin B1</subject><subject>Aflatoxins</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Carcinoma, Hepatocellular - chemically induced</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Chemical mutagenesis</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Mitochondrial - drug effects</subject><subject>Environmental aspects</subject><subject>Environmental Exposure - adverse effects</subject><subject>Environmental factors</subject><subject>Environmental Pollutants - toxicity</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Markers</subject><subject>Genomic analysis</subject><subject>Genomics</subject><subject>Hepatitis</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatoma</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Hépatology and Gastroenterology</subject><subject>Life Sciences</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mortality</subject><subject>Mutation</subject><subject>NRF2 protein</subject><subject>Oncology, 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spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome</title><author>Tanase, Anna-Maria ; Marchio, Agnès ; Dumitrascu, Traian ; Dima, Simona ; Herlea, Vlad ; Oprisan, Gabriela ; Dejean, Anne ; Popescu, Irinel ; Pineau, Pascal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c689t-50f7e15c7f78dd1b16cd4334ab2b6e9116931a2ae6b1ac9af3865b22d17ac9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>631/208/737</topic><topic>692/699/67/1504/1610</topic><topic>692/699/67/2324</topic><topic>704/172</topic><topic>Adult</topic><topic>Aflatoxin B1</topic><topic>Aflatoxins</topic><topic>Aged</topic><topic>Analysis</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Carcinoma, Hepatocellular - chemically induced</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Chemical mutagenesis</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Mitochondrial - drug effects</topic><topic>Environmental aspects</topic><topic>Environmental Exposure - adverse effects</topic><topic>Environmental factors</topic><topic>Environmental Pollutants - toxicity</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Markers</topic><topic>Genomic analysis</topic><topic>Genomics</topic><topic>Hepatitis</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatoma</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Hépatology and Gastroenterology</topic><topic>Life Sciences</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - chemically induced</topic><topic>Liver Neoplasms - genetics</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public 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of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome</atitle><jtitle>Journal of exposure science & environmental epidemiology</jtitle><stitle>J Expo Sci Environ Epidemiol</stitle><addtitle>J Expo Sci Environ Epidemiol</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>25</volume><issue>3</issue><spage>256</spage><epage>263</epage><pages>256-263</pages><issn>1559-0631</issn><eissn>1559-064X</eissn><abstract>Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (
NRF2
,
KEAP1
,
SRXN1
, and
CES1
) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for
β
-catenin and NRF2 (
P
<0.0001). Besides, tumors from patients born in Greater Bucharest carried
TP53
mutations more frequently than others (45
vs
10%,
P
=0.02). Finally, a R249S mutation of
TP53
, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>24736102</pmid><doi>10.1038/jes.2014.16</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-6541-5395</orcidid><orcidid>https://orcid.org/0000-0002-9407-1592</orcidid><orcidid>https://orcid.org/0000-0003-4778-6840</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1559-0631 |
| ispartof | Journal of exposure science & environmental epidemiology, 2015-05, Vol.25 (3), p.256-263 |
| issn | 1559-0631 1559-064X |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_pasteur_02863018v1 |
| source | Springer Nature |
| subjects | 631/208/737 692/699/67/1504/1610 692/699/67/2324 704/172 Adult Aflatoxin B1 Aflatoxins Aged Analysis Biochemistry, Molecular Biology Biomarkers, Tumor - genetics Cancer Carcinoma, Hepatocellular - chemically induced Carcinoma, Hepatocellular - genetics Chemical mutagenesis Deoxyribonucleic acid DNA DNA, Mitochondrial - drug effects Environmental aspects Environmental Exposure - adverse effects Environmental factors Environmental Pollutants - toxicity Epidemiology Female Gene expression Gene mutations Genes Genetic aspects Genetic Markers Genomic analysis Genomics Hepatitis Hepatocellular carcinoma Hepatoma Human health and pathology Humans Hépatology and Gastroenterology Life Sciences Liver cancer Liver Neoplasms - chemically induced Liver Neoplasms - genetics Male Medicine Medicine & Public Health Middle Aged Mitochondria Mortality Mutation NRF2 protein Oncology, Experimental original-article Oxidative stress Oxidative Stress - drug effects Oxidative Stress - genetics p53 Protein Point Mutation - drug effects Pollutants Prospective Studies Risk analysis Risk Factors Romania Tumors Western Europe β-Catenin |
| title | Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T12%3A53%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mutation%20spectrum%20of%20hepatocellular%20carcinoma%20from%20eastern-European%20patients%20betrays%20the%20impact%20of%20a%20complex%20exposome&rft.jtitle=Journal%20of%20exposure%20science%20&%20environmental%20epidemiology&rft.au=Tanase,%20Anna-Maria&rft.date=2015-05-01&rft.volume=25&rft.issue=3&rft.spage=256&rft.epage=263&rft.pages=256-263&rft.issn=1559-0631&rft.eissn=1559-064X&rft_id=info:doi/10.1038/jes.2014.16&rft_dat=%3Cgale_hal_p%3EA413180508%3C/gale_hal_p%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c689t-50f7e15c7f78dd1b16cd4334ab2b6e9116931a2ae6b1ac9af3865b22d17ac9f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1675143257&rft_id=info:pmid/24736102&rft_galeid=A413180508&rfr_iscdi=true |