NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene

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dc.contributor.author Mattila, Henna -
dc.contributor.author Schindler, Martin -
dc.contributor.author Isotalo, Jarkko -
dc.contributor.author Ikonen, Tarja -
dc.contributor.author Vihinen, Mauno -
dc.contributor.author Oja, Hannu -
dc.contributor.author Tammela, Teuvo L J -
dc.contributor.author Wahlfors, Tiina -
dc.contributor.author Schleutker, Johanna -
dc.date.accessioned 2012-06-17T20:14:21Z
dc.date.available 2012-06-15 07:19:27 -
dc.date.available 2012-06-17T20:14:21Z
dc.date.issued 2011 -
dc.identifier.issn 1471-2407 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65899
dc.description BioMed Central Open access -
dc.description.abstract Background Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified. Methods In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses were done using Agilent 44 K oligoarrays, and selected genes were screened for mutations by direct sequencing. In addition, microRNA expression levels in the lymphoblastic cells were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to PC. Results Seventeen genes were selected for resequencing based on the NMD array, but no truncating mutations were found. The most interesting variant was MAGEC1 p.Met1?. An association was seen between the variant and unselected PC (OR = 2.35, 95% CI = 1.10-5.02) and HPC (OR = 3.38, 95% CI = 1.10-10.40). miRNA analysis revealed altogether 29 miRNAs with altered expression between the PC cases and controls. miRNA target analysis revealed that 12 of them also had possible target sites in the MAGEC1 gene. These miRNAs were selected for validation process including four miRNAs located in the X chromosome. The expressions of 14 miRNAs were validated in families that contributed to the significant signal differences in Agilent arrays. Conclusions Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC. -
dc.language.iso en -
dc.title NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-660 -
dc.identifier.doi 10.1186/1471-2407-11-327 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Kirurgia, anestesiologia, tehohoito, radiologia | en=Surgery, Anesthesiology, Intensive Care| -
dc.administrativeunit fi=Terveystieteiden yksikkö | en=School of Health Sciences| -
dc.administrativeunit fi=Biolääketieteellisen teknologian yksikkö | en=Institute of Biomedical Technology| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title BMC Cancer -
dc.journal.volume 11 -
dc.journal.number 327 -
dc.journal.volumepagerange 1-11 -
dc.oldstats 69 -

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