DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis
The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear. We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs witho...
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| creator | Konishi, Kazuo Watanabe, Yoshiyuki Shen, Lanlan Guo, Yi Castoro, Ryan J Kondo, Kimie Chung, Woonbok Ahmed, Saira Jelinek, Jaroslav Boumber, Yanis A Estecio, Marcos R Maegawa, Shinji Kondo, Yutaka Itoh, Fumio Imawari, Michio Hamilton, Stanley R Issa, Jean-Pierre J |
| description | The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.
We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.
Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P |
| doi_str_mv | 10.1371/journal.pone.0027889 |
| format | Article |
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We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.
Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.
Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0027889</identifier><identifier>PMID: 22132162</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biology ; Bisulfite ; Cancer genetics ; Cancer metastasis ; Cell Line, Tumor ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; CpG islands ; CpG Islands - genetics ; Deactivation ; Density ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; DNA microarrays ; DNA Mutational Analysis ; E-cadherin ; Epigenetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes ; Genome, Human - genetics ; Health risk assessment ; Humans ; Inactivation ; Liver ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - secondary ; Male ; Medicine ; Metastases ; Methylation ; Middle Aged ; MLH1 protein ; Mutation ; Oligonucleotide Array Sequence Analysis ; Sulfites ; Tissue inhibitor of metalloproteinase 3 ; Tumors</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e27889-e27889</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Konishi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Konishi et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-52fb093e4de122327dd8eb6cce039cf63183c79954eaa0ceedc50540a4d437583</citedby><cites>FETCH-LOGICAL-c757t-52fb093e4de122327dd8eb6cce039cf63183c79954eaa0ceedc50540a4d437583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221680/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221680/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22132162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Wong, Chun-Ming</contributor><creatorcontrib>Konishi, Kazuo</creatorcontrib><creatorcontrib>Watanabe, Yoshiyuki</creatorcontrib><creatorcontrib>Shen, Lanlan</creatorcontrib><creatorcontrib>Guo, Yi</creatorcontrib><creatorcontrib>Castoro, Ryan J</creatorcontrib><creatorcontrib>Kondo, Kimie</creatorcontrib><creatorcontrib>Chung, Woonbok</creatorcontrib><creatorcontrib>Ahmed, Saira</creatorcontrib><creatorcontrib>Jelinek, Jaroslav</creatorcontrib><creatorcontrib>Boumber, Yanis A</creatorcontrib><creatorcontrib>Estecio, Marcos R</creatorcontrib><creatorcontrib>Maegawa, Shinji</creatorcontrib><creatorcontrib>Kondo, Yutaka</creatorcontrib><creatorcontrib>Itoh, Fumio</creatorcontrib><creatorcontrib>Imawari, Michio</creatorcontrib><creatorcontrib>Hamilton, Stanley R</creatorcontrib><creatorcontrib>Issa, Jean-Pierre J</creatorcontrib><title>DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.
We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.
Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.
Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biology</subject><subject>Bisulfite</subject><subject>Cancer genetics</subject><subject>Cancer metastasis</subject><subject>Cell Line, Tumor</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Deactivation</subject><subject>Density</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>DNA microarrays</subject><subject>DNA Mutational Analysis</subject><subject>E-cadherin</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genome, Human - genetics</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Inactivation</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - secondary</subject><subject>Male</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>MLH1 protein</subject><subject>Mutation</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Sulfites</subject><subject>Tissue inhibitor of metalloproteinase 3</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguLFjPlom_RGGNavgcUFdb0NZ9LTaYa0GZN2cf-9qdNdprIXkkAOyXPek5y8SfKckiXlgr7bucF3YJd71-GSECakLB8kp7TkbFEwwh8exSfJkxB2hORcFsXj5IQxyhkt2Gly9eHrKm2xb24s9MZ16d672lgMqatjbFrwN6l21nnUPdhUg9emcy2k0FVpC71usEqtuUY_ykCI04SnyaMabMBn03qWXH36-OP8y-Li8vP6fHWx0CIX_SJn9YaUHLMKKWOciaqSuCm0RsJLXRecSq5FWeYZAhCNWOmc5BmBrMq4yCU_S14edPfWBTV1JCjKKaG5ZLKMxPpAVA52anqQcmDU3w3ntwp8b7RFJUUFNI-lMwZZVlOJNRKmNwWKnHGootb7qdqwaeNdsOs92Jno_KQzjdq6a8VjvwtJosCbScC7XwOGXrUmaLQWOnRDUCWRhAhBeSRf_UPe_7iJ2kK8v-lqF8vqUVOtMlHIgpaFiNTyHiqOClujo3vG_54nvJ0lRKbH3_0WhhDU-vu3_2cvf87Z10dsg2D7Jjg7jL4LczA7gNq7EDzWdz2mRI3mv-2GGs2vJvPHtBfH_3OXdOt2_gcVsf99</recordid><startdate>20111121</startdate><enddate>20111121</enddate><creator>Konishi, Kazuo</creator><creator>Watanabe, Yoshiyuki</creator><creator>Shen, Lanlan</creator><creator>Guo, Yi</creator><creator>Castoro, Ryan J</creator><creator>Kondo, Kimie</creator><creator>Chung, Woonbok</creator><creator>Ahmed, Saira</creator><creator>Jelinek, Jaroslav</creator><creator>Boumber, Yanis A</creator><creator>Estecio, Marcos R</creator><creator>Maegawa, Shinji</creator><creator>Kondo, Yutaka</creator><creator>Itoh, Fumio</creator><creator>Imawari, Michio</creator><creator>Hamilton, Stanley R</creator><creator>Issa, Jean-Pierre J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111121</creationdate><title>DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis</title><author>Konishi, Kazuo ; Watanabe, Yoshiyuki ; Shen, Lanlan ; Guo, Yi ; Castoro, Ryan J ; Kondo, Kimie ; Chung, Woonbok ; Ahmed, Saira ; Jelinek, Jaroslav ; Boumber, Yanis A ; Estecio, Marcos R ; Maegawa, Shinji ; Kondo, Yutaka ; Itoh, Fumio ; Imawari, Michio ; Hamilton, Stanley R ; Issa, Jean-Pierre J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-52fb093e4de122327dd8eb6cce039cf63183c79954eaa0ceedc50540a4d437583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biology</topic><topic>Bisulfite</topic><topic>Cancer genetics</topic><topic>Cancer metastasis</topic><topic>Cell Line, Tumor</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>Deactivation</topic><topic>Density</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>DNA microarrays</topic><topic>DNA Mutational Analysis</topic><topic>E-cadherin</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genome, Human - genetics</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Inactivation</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - secondary</topic><topic>Male</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>MLH1 protein</topic><topic>Mutation</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Sulfites</topic><topic>Tissue inhibitor of metalloproteinase 3</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Konishi, Kazuo</creatorcontrib><creatorcontrib>Watanabe, Yoshiyuki</creatorcontrib><creatorcontrib>Shen, Lanlan</creatorcontrib><creatorcontrib>Guo, Yi</creatorcontrib><creatorcontrib>Castoro, Ryan J</creatorcontrib><creatorcontrib>Kondo, Kimie</creatorcontrib><creatorcontrib>Chung, Woonbok</creatorcontrib><creatorcontrib>Ahmed, Saira</creatorcontrib><creatorcontrib>Jelinek, Jaroslav</creatorcontrib><creatorcontrib>Boumber, Yanis A</creatorcontrib><creatorcontrib>Estecio, Marcos R</creatorcontrib><creatorcontrib>Maegawa, Shinji</creatorcontrib><creatorcontrib>Kondo, Yutaka</creatorcontrib><creatorcontrib>Itoh, Fumio</creatorcontrib><creatorcontrib>Imawari, Michio</creatorcontrib><creatorcontrib>Hamilton, Stanley R</creatorcontrib><creatorcontrib>Issa, Jean-Pierre J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Konishi, Kazuo</au><au>Watanabe, Yoshiyuki</au><au>Shen, Lanlan</au><au>Guo, Yi</au><au>Castoro, Ryan J</au><au>Kondo, Kimie</au><au>Chung, Woonbok</au><au>Ahmed, Saira</au><au>Jelinek, Jaroslav</au><au>Boumber, Yanis A</au><au>Estecio, Marcos R</au><au>Maegawa, Shinji</au><au>Kondo, Yutaka</au><au>Itoh, Fumio</au><au>Imawari, Michio</au><au>Hamilton, Stanley R</au><au>Issa, Jean-Pierre J</au><au>Wong, Chun-Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-21</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e27889</spage><epage>e27889</epage><pages>e27889-e27889</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.
We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.
Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.
Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22132162</pmid><doi>10.1371/journal.pone.0027889</doi><tpages>e27889</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-11, Vol.6 (11), p.e27889-e27889 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1310158289 |
| source | PubMed Central Free; MEDLINE; Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Aged, 80 and over Biology Bisulfite Cancer genetics Cancer metastasis Cell Line, Tumor Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics CpG islands CpG Islands - genetics Deactivation Density Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics DNA microarrays DNA Mutational Analysis E-cadherin Epigenetics Female Gene Expression Regulation, Neoplastic Genes Genome, Human - genetics Health risk assessment Humans Inactivation Liver Liver cancer Liver Neoplasms - genetics Liver Neoplasms - secondary Male Medicine Metastases Methylation Middle Aged MLH1 protein Mutation Oligonucleotide Array Sequence Analysis Sulfites Tissue inhibitor of metalloproteinase 3 Tumors |
| title | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T22%3A55%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20methylation%20profiles%20of%20primary%20colorectal%20carcinoma%20and%20matched%20liver%20metastasis&rft.jtitle=PloS%20one&rft.au=Konishi,%20Kazuo&rft.date=2011-11-21&rft.volume=6&rft.issue=11&rft.spage=e27889&rft.epage=e27889&rft.pages=e27889-e27889&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0027889&rft_dat=%3Cgale_plos_%3EA476861967%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1310158289&rft_id=info:pmid/22132162&rft_galeid=A476861967&rft_doaj_id=oai_doaj_org_article_87da15e0342a44f18efe02cb6e7523ad&rfr_iscdi=true |