Show simple item record

dc.contributor.authorLuedeke, M
dc.contributor.authorRinckleb, AE
dc.contributor.authorFitzGerald, LM
dc.contributor.authorGeybels, MS
dc.contributor.authorSchleutker, J
dc.contributor.authorEeles, RA
dc.contributor.authorTeixeira, MR
dc.contributor.authorCannon-Albright, L
dc.contributor.authorOstrander, EA
dc.contributor.authorWeikert, S
dc.contributor.authorHerkommer, K
dc.contributor.authorWahlfors, T
dc.contributor.authorVisakorpi, T
dc.contributor.authorLeinonen, KA
dc.contributor.authorTammela, TLJ
dc.contributor.authorCooper, CS
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorEdwards, S
dc.contributor.authorGoh, CL
dc.contributor.authorMcCarthy, F
dc.contributor.authorParker, C
dc.contributor.authorFlohr, P
dc.contributor.authorPaulo, P
dc.contributor.authorJerónimo, C
dc.contributor.authorHenrique, R
dc.contributor.authorKrause, H
dc.contributor.authorWach, S
dc.contributor.authorLieb, V
dc.contributor.authorRau, TT
dc.contributor.authorVogel, W
dc.contributor.authorKuefer, R
dc.contributor.authorHofer, MD
dc.contributor.authorPerner, S
dc.contributor.authorRubin, MA
dc.contributor.authorAgarwal, AM
dc.contributor.authorEaston, DF
dc.contributor.authorAl Olama, AA
dc.contributor.authorBenlloch, S
dc.contributor.authorPRACTICAL consortium
dc.contributor.authorHoegel, J
dc.contributor.authorStanford, JL
dc.contributor.authorMaier, C
dc.date.accessioned2016-11-23T15:37:38Z
dc.date.issued2016-12
dc.identifier.citationHuman molecular genetics, 2016, 25 (24), pp. 5490 - 5499
dc.identifier.issn0964-6906
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/272
dc.identifier.eissn1460-2083
dc.identifier.doi10.1093/hmg/ddw349
dc.description.abstractMolecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa.
dc.formatPrint
dc.format.extent5490 - 5499
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPRACTICAL consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectSerine Endopeptidases
dc.subjectOncogene Proteins, Fusion
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGenotype
dc.subjectQuantitative Trait Loci
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectTranscriptional Regulator ERG
dc.titleProstate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status.
dc.typeJournal Article
dcterms.dateAccepted2016-10-07
rioxxterms.versionofrecord10.1093/hmg/ddw349
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHuman molecular genetics
pubs.issue24
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume25
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorParker, Chrisen
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


Files in this item

Thumbnail
Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0