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dc.contributor.authorSilva, Leonarden_US
dc.contributor.authorSimpson, Peteren_US
dc.contributor.authorSmart, Chanelen_US
dc.contributor.authorCocciardi, Sibylleen_US
dc.contributor.authorWaddell, Nicen_US
dc.contributor.authorLane, Annetteen_US
dc.contributor.authorMorrison, Brianen_US
dc.contributor.authorVargas, Ana Cristinaen_US
dc.contributor.authorHealey, Sueen_US
dc.contributor.authorBeesley, Jonathanen_US
dc.contributor.authorPakkiri, Priaen_US
dc.contributor.authorParry, Suzanneen_US
dc.contributor.authorKurniawan, Nyomanen_US
dc.contributor.authorReid, Lynneen_US
dc.contributor.authorKeith, Patriciaen_US
dc.contributor.authorFaria, Pauloen_US
dc.contributor.authorPereira, Emilioen_US
dc.contributor.authorSkalova, Alenaen_US
dc.contributor.authorBilous, Michaelen_US
dc.contributor.authorBalleine, Rosemaryen_US
dc.contributor.authorDo, Hongdoen_US
dc.contributor.authorDobrovic, Alexanderen_US
dc.contributor.authorFox, Stephenen_US
dc.contributor.authorFranco, Marcelloen_US
dc.contributor.authorReynolds, Brenten_US
dc.contributor.authorKhanna, Kum Kumen_US
dc.contributor.authorChenevix-Trench, Georgiaen_US
dc.contributor.authorLakhani, Sunilen_US
dc.date.accessioned2017-05-03T13:11:44Z
dc.date.available2017-05-03T13:11:44Z
dc.date.issued2010en_US
dc.date.modified2012-09-10T22:35:43Z
dc.identifier.issn14655411en_US
dc.identifier.doi10.1186/bcr2603en_US
dc.identifier.urihttp://hdl.handle.net/10072/38750
dc.description.abstractIntroduction: Metastases to the brain from breast cancer have a high mortality, and basal-like breast cancers have a propensity for brain metastases. However, the mechanisms that allow cells to colonize the brain are unclear. Methods: We used morphology, immunohistochemistry, gene expression and somatic mutation profiling to analyze 39 matched pairs of primary breast cancers and brain metastases, 22 unmatched brain metastases of breast cancer, 11 non-breast brain metastases and 6 autopsy cases of patients with breast cancer metastases to multiple sites, including the brain. Results: Most brain metastases were triple negative and basal-like. The brain metastases over-expressed one or more members of the HER family and in particular HER3 was significantly over-expressed relative to matched primary tumors. Brain metastases from breast and other primary sites, and metastases to multiple organs in the autopsied cases, also contained somatic mutations in EGFR, HRAS, KRAS, NRAS or PIK3CA. This paralleled the frequent activation of AKT and MAPK pathways. In particular, activation of the MAPK pathway was increased in the brain metastases compared to the primary tumors. Conclusions: Deregulated HER family receptors, particularly HER3, and their downstream pathways are implicated in colonization of brain metastasis. The need for HER family receptors to dimerize for activation suggests that tumors may be susceptible to combinations of anti-HER family inhibitors, and may even be effective in the absence of HER2 amplification (that is, in triple negative/basal cancers). However, the presence of activating mutations ien_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.format.extent1788905 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherBioMed Centralen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefromR46-1en_US
dc.relation.ispartofpagetoR46-13en_US
dc.relation.ispartofissue4en_US
dc.relation.ispartofjournalBreast Cancer Researchen_US
dc.relation.ispartofvolume12en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchCancer Cell Biologyen_US
dc.subject.fieldofresearchcode111201en_US
dc.titleHER3 and downstream pathways are involved in colonization of brain metastases from breast canceren_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dcterms.licensehttp://creativecommons.org/licenses/by/2.0en_US
gro.description.notepublicPage numbers are not for citation purposes. Instead, this article has the unique article number of 12.en_US
gro.rights.copyrightCopyright 2010 Silva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
gro.date.issued2010
gro.hasfulltextFull Text


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