DNA methylation in the placenta and in cancerwith special reference to folate transporting genes

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Fältnamn	Indikatorer	Metadata
000		04174nam a2200481 4500
001		oai:DiVA.org:oru-32599
003		SwePub
008		131202s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
020		a 9789176689868q print
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-325992 URI
040		a (SwePub)oru
041		a engb eng
042		9 SwePub
072	7	a vet2 swepub-contenttype
072	7	a dok2 swepub-publicationtype
100	1	a Farkas, Sanja,d 1983-u Örebro universitet,Institutionen för hälsovetenskap och medicin4 aut0 (Swepub:oru)sfs
245	1 0	a DNA methylation in the placenta and in cancerwith special reference to folate transporting genes
264	1	a Örebro :b Örebro university,c 2014
300		a 67 s.
338		a electronic2 rdacarrier
490	0	a Örebro Studies in Medicine,x 1652-4063 ;v 100
520		a 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
653		a DNA methylation
653		a CRC
653		a placenta
653		a cervix
653		a leukocytes
653		a T-DMRs
653		a folate
653		a array
653		a expression
653		a Biomedicin
653		a Biomedicine
700	1	a Nilsson, Torbjörn,c Professoru Örebro universitet,Institutionen för hälsovetenskap och medicin4 ths0 (Swepub:oru)tnnn
700	1	a Breimer, Lars,c Dru Laboratoriemedicinska länskliniken, Örebro university hospital, Örebro, Sweden4 ths
700	1	a Kruger, Warren D.,c Professoru Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-24974 opn
710	2	a Örebro universitetb Institutionen för hälsovetenskap och medicin4 org
856	4	u https://oru.diva-portal.org/smash/get/diva2:668943/FULLTEXT02.pdfx primaryx Raw objecty fulltext
856	4	u https://oru.diva-portal.org/smash/get/diva2:668943/COVER01.pdfy cover
856	4	u https://oru.diva-portal.org/smash/get/diva2:668943/SPIKBLAD01.pdfy spikblad
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-32599

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