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dc.contributor.authorDa Silva, Leonard
dc.contributor.authorSimpson, Peter T
dc.contributor.authorSmart, Chanel E
dc.contributor.authorCocciardi, Sibylle
dc.contributor.authorWaddell, Nic
dc.contributor.authorLane, Annette
dc.contributor.authorMorrison, Brian J
dc.contributor.authorVargas, Ana Cristina
dc.contributor.authorHealey, Sue
dc.contributor.authorBeesley, Jonathan
dc.contributor.authorPakkiri, Pria
dc.contributor.authorParry, Suzanne
dc.contributor.authorKurniawan, Nyoman
dc.contributor.authorReid, Lynne
dc.contributor.authorKeith, Patricia
dc.contributor.authorFaria, Paulo
dc.contributor.authorPereira, Emilio
dc.contributor.authorSkalova, Alena
dc.contributor.authorBilous, Michael
dc.contributor.authorBalleine, Rosemary L
dc.contributor.authorDo, Hongdo
dc.contributor.authorDobrovic, Alexander
dc.contributor.authorFox, Stephen
dc.contributor.authorFranco, Marcello
dc.contributor.authorReynolds, Brent
dc.contributor.authorKhanna, Kum Kum
dc.contributor.authorCummings, Margaret
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorLakhani, Sunil R
dc.date.accessioned2017-05-03T13:11:44Z
dc.date.available2017-05-03T13:11:44Z
dc.date.issued2010
dc.date.modified2012-09-10T22:35:43Z
dc.identifier.issn1465-5411
dc.identifier.doi10.1186/bcr2603
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 i
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1788905 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefromR46-1
dc.relation.ispartofpagetoR46-13
dc.relation.ispartofissue4
dc.relation.ispartofjournalBreast Cancer Research
dc.relation.ispartofvolume12
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer cell biology
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321101
dc.titleHER3 and downstream pathways are involved in colonization of brain metastases from breast cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/2.0
gro.description.notepublicPage numbers are not for citation purposes. Instead, this article has the unique article number of 12.
gro.rights.copyright© 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.
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorMorrison, Brian


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