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WFRF:(Lothe Ragnhild A)
 

Sökning: WFRF:(Lothe Ragnhild A) > Regulator of Chromo...

  • Bruun, JarleOslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway (författare)

Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer

  • Artikel/kapitelEngelska2015

Förlag, utgivningsår, omfång ...

  • AMER ASSOC CANCER RESEARCH,2015
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-122121
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122121URI
  • https://doi.org/10.1158/1078-0432.CCR-14-3294DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:132042962URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Norwegian Cancer Society [PR-2006-0442, PR-2007-0166]; South-Eastern Norway Regional Health Authority
  • Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kolberg, MatthiasOslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway (författare)
  • Ahlquist, Terje C.Oslo University Hospital, Norway; Oslo University Hospital, Norway (författare)
  • Royrvik, Ellen C.Oslo University Hospital, Norway; University of Oslo, Norway; University of Oxford, England (författare)
  • Nome, TorfinnOslo University Hospital, Norway; University of Oslo, Norway (författare)
  • Leithe, EdwardOslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway (författare)
  • Lind, Guro E.Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway (författare)
  • Merok, Marianne A.Oslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway (författare)
  • Rognum, Torleiv O.University of Oslo, Norway; Norwegian Institute Public Heatlh, Norway (författare)
  • Bjorkoy, GeirUniversity of Coll Sor Trondelag, Norway (författare)
  • Johansen, TerjeUniversity of Tromso, Norway (författare)
  • Lindblom, AnnikaKarolinska Institutet (författare)
  • Sun, Xiao-FengLinköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)xiasu45 (författare)
  • Svindland, AudUniversity of Oslo, Norway; Oslo University Hospital, Norway (författare)
  • Liestol, KnutUniversity of Oslo, Norway; Fac Math and Nat Science, Norway (författare)
  • Nesbakken, ArildOslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway; University of Oslo, Norway (författare)
  • Skotheim, Rolf I.Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; Fac Math and Nat Science, Norway (författare)
  • Lothe, Ragnhild A.Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway (författare)
  • Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, NorwayOslo University Hospital, Norway; Oslo University Hospital, Norway (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Clinical Cancer Research: AMER ASSOC CANCER RESEARCH21:16, s. 3759-37701078-04321557-3265

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