oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome-wide DNA methylation assay reveals novel candidate biomarker genes in cervical cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
Dept Mol Med, Rudjer Boskovic Inst, Zagreb, Croatia.
Dept Mol Med, Rudjer Boskovic Inst, Zagreb, Croatia.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2013 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 8, no 11, 1213-1225 p.Article in journal (Refereed) Published
Abstract [en]

The oncogenic human papilloma viruses (HPVs) are associated with precancerous cervical lesions and development of cervical cancer. The DNA methylation signatures of the host genome in normal, precancerous and cervical cancer tissue may indicate tissue-specific perturbation in carcinogenesis. The aim of this study was to identify new candidate genes that are differentially methylated in squamous cell carcinoma compared with DNA samples from cervical intraepithelial neoplasia grade 3 (CIN3) and normal cervical scrapes. The Illumina Infinium HumanMethylation450 BeadChip method identifies genome-wide DNA methylation changes in CpG islands, CpG shores and shelves. Our findings showed an extensive differential methylation signature in cervical cancer compared with the CIN3 or normal cervical tissues. The identified candidate biomarker genes for cervical cancer represent several types of mechanisms in the cellular machinery that are epigenetically deregulated by hypermethylation, such as membrane receptors, intracellular signaling and gene transcription. The results also confirm extensive hypomethylation of genes in the immune system in cancer tissues. These insights into the functional role of DNA methylome alterations in cervical cancer could be clinically applicable in diagnostics and prognostics, and may guide the development of new epigenetic therapies.

Place, publisher, year, edition, pages
2013. Vol. 8, no 11, 1213-1225 p.
Keyword [en]
DNA methylation, Infinium Human Methylation 450 BeadChip, HPV, cervical cancer, immune system
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-35866DOI: 10.4161/epi.26346ISI: 000336517500010OAI: oai:DiVA.org:oru-35866DiVA: diva2:736546
Note

Funding agencies:

Lions Cancer Foundation

Nyckelfonden  

Orebro lans landsting  

Croatian Ministry of Science, Education and Sports, grant number 098-0982464-2510 

Available from: 2014-08-07 Created: 2014-08-07 Last updated: 2017-10-18Bibliographically approved
In thesis
1. DNA methylation in the placenta and in cancerwith special reference to folate transporting genes
Open this publication in new window or tab >>DNA methylation in the placenta and in cancerwith special reference to folate transporting genes
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

DNA methylation is an epigenetic mechanism that regulates the gene transcription. Folate is used in cellular synthesis of methyl groups, nucleic acids and amino acids. In complex diseases like cancer and neural tube defects (NTD), various genetic and epigenetic alterations can be found that disrupt the normal cell function. The main goals of this thesis were to analyze whether the genes responsible for the folate transport (FOLR1, PCFT, and RFC1) could be regulated by DNA methylation in placenta, blood leukocytes and colorectal cancer. We also addressed the genome-wide DNA methylation changes in colorectal cancer andcervical cancer.We found that changes in the methylated fraction of the RFC1 gene were dependent on the RFC1 80G>A polymorphism in placental specimens with NTDs and blood leukocytes from subjects with high homocysteine (Paper I). In colorectal cancer, the greatest difference in DNA methylation was observed in the RFC1 gene and was related to a lower protein expression (Paper II).In Paper III and IV we studied the DNA methylated fraction using a high-density array. Paper III was focused on genes in the DNA repair pathway and frequently mutated in colorectal cancer. We found that aberrant methylation in the DNA mismatch repair genes was not a frequent event in colorectal cancer and we identified five candidate biomarker genes in colorectal cancer, among them the GPC6 and DCLRE1C genes. In Paper IV, we found hypomethylation of genes involved in the immune system in cervical cancer specimens compared to healthy cervical scrapes and we identified twenty four candidate genes for further evaluation ofclinical value.In conclusion, the work of this thesis filled a relevant knowledge gap regarding the role of differential methylation of the folate transport genes in NTD and colorectal cancer. This thesis work also provided insights into the functional role of DNA methylation in cancer specific pathways and identified potential novel biomarker genes.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2014. 67 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 100
Keyword
DNA methylation, CRC, placenta, cervix, leukocytes, T-DMRs, folate, array, expression
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-32599 (URN)978-91-7668-986-8 (ISBN)
Public defence
2014-01-31, Wilandersalen, Universitetssjukhuset, S. Grev Rosengatan, 703 62 Örebro, 09:15 (English)
Opponent
Supervisors
Available from: 2013-12-02 Created: 2013-12-02 Last updated: 2017-10-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Farkas, Sanja A.Nilsson, Torbjorn K.
By organisation
School of Health and Medical Sciences, Örebro University, SwedenÖrebro University Hospital
In the same journal
Epigenetics
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 25 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf