1. DIGITAL.CSIC
  2. Biología y Biomedicina
  3. Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM)
  4. (IIBM) Artículos
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/150908
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE

Comparte tu historia
de Acceso Abierto
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Campo DC Valor Lengua/Idioma
dc.contributor.authorHellner, Karin-
dc.contributor.authorMota, Alba-
dc.contributor.authorMoreno-Bueno, Gema-
dc.contributor.authorMatías-Guiu, Xavier-
dc.contributor.authorBenítez, Javier-
dc.contributor.authorAshour Ahmed, Ahmed-
dc.date.accessioned2017-06-05T10:10:43Z-
dc.date.available2017-06-05T10:10:43Z-
dc.date.issued2016-
dc.identifierdoi: 10.1016/j.ebiom.2016.06.048-
dc.identifiere-issn: 2352-3964-
dc.identifier.citationEBioMedicine 10: 137-149 (2016)-
dc.identifier.urihttp://hdl.handle.net/10261/150908-
dc.descriptionOpen Access funded by Medical Research Council. Under a Creative Commons license.-- et al.-
dc.description.abstractCurrent screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p<2(-16)), which was not found in patients without cancer (n=108). Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n=100), and common in BRCA1-BRCA2 mutation carriers (n=71) who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.-
dc.description.sponsorshipThis work is funded by the Medical Research Council (H8RSRS00), Ovarian Cancer Action (HER00070), the Oxford Biomedical Research Centre, the National Institute for Health Research (HJRWAC05) and the Experimental Cancer Medicine Centre. MJG is recipient of a research contract from the Instituto de Salud Carlos III of the Ministerio Español de Sanidad y Consumo (Miguel Servet tipo II Program, CPII 13-00047). C.Y. acknowledges the support of an MRC New Investigator Research Grant (Ref No. MR-L001411-1) and the Wellcome Trust Core Award Grant Number 090532-Z-09-Z.-
dc.publisherElsevier-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.subjectPrecancer-
dc.subjectFallopian tube-
dc.subjectBRCA mutations-
dc.subjectSOX2-
dc.subjectScreening-
dc.subjectOvarian cancer-
dc.titlePremalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies-
dc.typeartículo-
dc.identifier.doi10.1016/j.ebiom.2016.06.048-
dc.relation.publisherversionhttps://doi.org/10.1016/j.ebiom.2016.06.048-
dc.date.updated2017-06-05T10:10:43Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/-
dc.contributor.funderMedical Research Council (UK)-
dc.contributor.funderUniversity of Oxford-
dc.contributor.funderNational Institute for Health Research (UK)-
dc.contributor.funderMinisterio de Sanidad y Consumo (España)-
dc.contributor.funderWellcome Trust-
dc.contributor.funderInstituto de Salud Carlos III-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000265es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000769es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000272es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100004440es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.pmid27492892-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.cerifentitytypePublications-
item.openairetypeartículo-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato
PremalignantSOX2.pdf1,56 MBAdobe PDFVista previa
Visualizar/Abrir
Show simple item record

CORE Recommender

PubMed Central
Citations

22
checked on 25-abr-2024

SCOPUSTM   
Citations

30
checked on 23-abr-2024

WEB OF SCIENCETM
Citations

29
checked on 25-feb-2024

Page view(s)

301
checked on 24-abr-2024

Download(s)

332
checked on 24-abr-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


Este item está licenciado bajo una Licencia Creative Commons Creative Commons