Impact of RASSF1A gene methylation on the metastatic axillary nodal status in breast cancer patients
Identifieur interne : 000497 ( Main/Exploration ); précédent : 000496; suivant : 000498Impact of RASSF1A gene methylation on the metastatic axillary nodal status in breast cancer patients
Auteurs : Eva Jezkova [Slovaquie] ; Pavol Zubor [Slovaquie] ; Karol Kajo [Slovaquie] ; Marian Grendar [Slovaquie] ; Karol Dokus [Slovaquie] ; Marian Adamkov [Slovaquie] ; Zora Lasabova [Slovaquie] ; Lukas Plank [Slovaquie] ; Jan Danko [Slovaquie]Source :
- Oncology Letters [ 1792-1074 ] ; 2017.
Abstract
Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, the present study focused on the DNA methylation profile of invasive breast carcinoma. The aim of the study was to evaluate the prognostic significance of Ras association domain family 1 isoform A (
Url:
DOI: 10.3892/ol.2017.6204
PubMed: 28693231
PubMed Central: 5494671
Affiliations:
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sortKey="Adamkov, Marian" sort="Adamkov, Marian" uniqKey="Adamkov M" first="Marian" last="Adamkov">Marian Adamkov</name><affiliation wicri:level="1"><nlm:aff id="af2-ol-0-0-6204">Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Lasabova, Zora" sort="Lasabova, Zora" uniqKey="Lasabova Z" first="Zora" last="Lasabova">Zora Lasabova</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-6204">Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Plank, Lukas" sort="Plank, Lukas" uniqKey="Plank L" first="Lukas" last="Plank">Lukas Plank</name><affiliation wicri:level="1"><nlm:aff id="af6-ol-0-0-6204">Department of Pathological Anatomy, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Pathological Anatomy, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Danko, Jan" sort="Danko, Jan" uniqKey="Danko J" first="Jan" last="Danko">Jan Danko</name><affiliation wicri:level="1"><nlm:aff id="af3-ol-0-0-6204">Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28693231</idno><idno type="pmc">5494671</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494671</idno><idno type="RBID">PMC:5494671</idno><idno type="doi">10.3892/ol.2017.6204</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">004249</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004249</idno><idno type="wicri:Area/Pmc/Curation">004248</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004248</idno><idno type="wicri:Area/Pmc/Checkpoint">000247</idno><idno 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xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-ol-0-0-6204">Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Zubor, Pavol" sort="Zubor, Pavol" uniqKey="Zubor P" first="Pavol" last="Zubor">Pavol Zubor</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-6204">Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-ol-0-0-6204">Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Kajo, Karol" sort="Kajo, Karol" uniqKey="Kajo K" first="Karol" last="Kajo">Karol Kajo</name><affiliation wicri:level="1"><nlm:aff id="af4-ol-0-0-6204">St. Elizabeth Cancer Institute Hospital, 812 50 Bratislava, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>St. Elizabeth Cancer Institute Hospital, 812 50 Bratislava</wicri:regionArea><wicri:noRegion>812 50 Bratislava</wicri:noRegion></affiliation></author><author><name sortKey="Grendar, Marian" sort="Grendar, Marian" uniqKey="Grendar M" first="Marian" last="Grendar">Marian Grendar</name><affiliation wicri:level="1"><nlm:aff id="af5-ol-0-0-6204">Bioinformatic Unit, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Bioinformatic Unit, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Dokus, Karol" sort="Dokus, Karol" uniqKey="Dokus K" first="Karol" last="Dokus">Karol Dokus</name><affiliation wicri:level="1"><nlm:aff id="af3-ol-0-0-6204">Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Adamkov, Marian" sort="Adamkov, Marian" uniqKey="Adamkov M" first="Marian" last="Adamkov">Marian Adamkov</name><affiliation wicri:level="1"><nlm:aff id="af2-ol-0-0-6204">Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Lasabova, Zora" sort="Lasabova, Zora" uniqKey="Lasabova Z" first="Zora" last="Lasabova">Zora Lasabova</name><affiliation wicri:level="1"><nlm:aff id="af1-ol-0-0-6204">Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Plank, Lukas" sort="Plank, Lukas" uniqKey="Plank L" first="Lukas" last="Plank">Lukas Plank</name><affiliation wicri:level="1"><nlm:aff id="af6-ol-0-0-6204">Department of Pathological Anatomy, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Pathological Anatomy, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author><author><name sortKey="Danko, Jan" sort="Danko, Jan" uniqKey="Danko J" first="Jan" last="Danko">Jan Danko</name><affiliation wicri:level="1"><nlm:aff id="af3-ol-0-0-6204">Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin, Slovakia</nlm:aff><country xml:lang="fr">Slovaquie</country><wicri:regionArea>Department of Obstetrics and Gynaecology, Jessenius Faculty of Medicine, Martin University Hospital, 036 01 Martin</wicri:regionArea><wicri:noRegion>036 01 Martin</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncology Letters</title><idno type="ISSN">1792-1074</idno><idno type="eISSN">1792-1082</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, the present study focused on the DNA methylation profile of invasive breast carcinoma. The aim of the study was to evaluate the prognostic significance of Ras association domain family 1 isoform A (<italic>RASSF1A</italic>) promoter methylation status in operable breast cancer, and to analyze the utility of this biomarker regarding its association with metastatic and nonmetastatic axillary nodal status. For this purpose, formalin-fixed, paraffin-embedded tissue specimens from 116 breast cancer patients with known axillary nodal status were subjected to assessment of <italic>RASSF1A</italic> promoter methylation status by methylation-specific polymerase chain reaction (MSP) and methylation-sensitive high-resolution melting assay, and the results were subsequently validated by bisulfite sequencing. A multinomial logistic regression model was used to model the dependence of distinct levels of methylation status of the <italic>RASSF1A</italic> promoter on the nodal status. Promoter region CpG hypermethylation was identified by MSP in 97 (83.6%) of 116 primary breast tumors, while hypermethylation of <italic>RASSF1A</italic> was confirmed by MS-HRM in 107 (92.2%) of 116 cases of breast cancer. Based on the results of the multinomial logistic regression model, there was no significant difference between the frequency of <italic>RASSF1A</italic> promoter methylation and axillary lymph node status of patients in general. However, upon adjustment of pN stage, an association was identified between pN0 lymph node-negative status (without axillary metastases) and percentage of <italic>RASSF1A</italic> methylation in two groups of heterogeneous methylated alleles with ≤50% methylated (P<0.05) and >50% methylated alleles (P<0.0001). If a patients' nodal status changes from pN- to pN+ then the risk of having >50% methylated alleles increases by 7%. The present study revealed a specific phenomenon, suggesting that the presence of heterogeneous methylated alleles in the <italic>RASSF1A</italic> gene is significantly associated with lymph node-negative status in breast cancer patients. Furthermore, greater significance with negative axillary nodal status was observed with a higher level of heterogeneous methylated alleles in the <italic>RASSF1A</italic> gene.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tao, Z" uniqKey="Tao Z">Z Tao</name></author><author><name sortKey="Shi, A" uniqKey="Shi A">A Shi</name></author><author><name sortKey="Lu, C" uniqKey="Lu C">C Lu</name></author><author><name sortKey="Song, T" uniqKey="Song T">T Song</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lester, Sc" uniqKey="Lester S">SC Lester</name></author><author><name sortKey="Hicks, Dg" uniqKey="Hicks D">DG Hicks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lyman, Gh" uniqKey="Lyman G">GH 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Karol" uniqKey="Dokus K" first="Karol" last="Dokus">Karol Dokus</name><name sortKey="Grendar, Marian" sort="Grendar, Marian" uniqKey="Grendar M" first="Marian" last="Grendar">Marian Grendar</name><name sortKey="Jezkova, Eva" sort="Jezkova, Eva" uniqKey="Jezkova E" first="Eva" last="Jezkova">Eva Jezkova</name><name sortKey="Kajo, Karol" sort="Kajo, Karol" uniqKey="Kajo K" first="Karol" last="Kajo">Karol Kajo</name><name sortKey="Lasabova, Zora" sort="Lasabova, Zora" uniqKey="Lasabova Z" first="Zora" last="Lasabova">Zora Lasabova</name><name sortKey="Plank, Lukas" sort="Plank, Lukas" uniqKey="Plank L" first="Lukas" last="Plank">Lukas Plank</name><name sortKey="Zubor, Pavol" sort="Zubor, Pavol" uniqKey="Zubor P" first="Pavol" last="Zubor">Pavol Zubor</name><name sortKey="Zubor, Pavol" sort="Zubor, Pavol" uniqKey="Zubor P" first="Pavol" last="Zubor">Pavol Zubor</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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