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dc.contributor.authorMiller, Michael B.en_US
dc.contributor.authorBi, Wenya Lindaen_US
dc.contributor.authorRamkissoon, Lori A.en_US
dc.contributor.authorKang, Yun Jeeen_US
dc.contributor.authorAbedalthagafi, Malaken_US
dc.contributor.authorKnoff, David S.en_US
dc.contributor.authorAgarwalla, Pankaj K.en_US
dc.contributor.authorWen, Patrick Y.en_US
dc.contributor.authorReardon, David A.en_US
dc.contributor.authorAlexander, Brian M.en_US
dc.contributor.authorLaws, Edward R.en_US
dc.contributor.authorDunn, Ian F.en_US
dc.contributor.authorBeroukhim, Rameenen_US
dc.contributor.authorLigon, Keith L.en_US
dc.contributor.authorRamkissoon, Shakti H.en_US
dc.date.accessioned2016-12-02T15:24:44Z
dc.date.issued2016en_US
dc.identifier.citationMiller, M. B., W. L. Bi, L. A. Ramkissoon, Y. J. Kang, M. Abedalthagafi, D. S. Knoff, P. K. Agarwalla, et al. 2016. “MAPK activation and HRAS mutation identified in pituitary spindle cell oncocytoma.” Oncotarget 7 (24): 37054-37063. doi:10.18632/oncotarget.9244. http://dx.doi.org/10.18632/oncotarget.9244.en
dc.identifier.issn1949-2553en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29626074
dc.description.abstractPituitary spindle cell oncocytoma (SCO) is an uncommon primary pituitary neoplasm that presents with mass effect on adjacent neurovascular structures, similar to non-hormone-producing pituitary adenomas. To determine the molecular etiology of SCO, we performed exome sequencing on four SCO cases, with matched normal controls, to assess somatic mutations and copy number alterations. Our analysis revealed a low mutation rate and a copy-neutral profile, consistent with the low-grade nature of this tumor. However, we identified a co-occurring somatic HRAS (p.Q61R) activating point mutation and MEN1 frameshift mutation (p.L117fs) present in a primary and recurrent tumor from one patient. Other SCOs demonstrated mutations in SND1 and FAT1, which are associated with MAPK pathway activation. Immunohistochemistry across the SCO cohort demonstrated robust MAPK activity in all cases (n=4), as evidenced by strong phospho-ERK staining, while phospho-AKT levels suggested only basal levels of PI3K pathway activation. Taken together, this identifies the MAPK signaling pathway as a novel therapeutic target for spindle cell oncocytoma, which may offer a powerful adjunct for aggressive tumors refractory to surgical resection.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.isversionofdoi:10.18632/oncotarget.9244en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095058/pdf/en
dash.licenseLAAen_US
dc.subjectspindle cell oncocytomaen
dc.subjectpituitaryen
dc.subjectMAPKen
dc.subjectHRASen
dc.subjectgenomicsen
dc.titleMAPK activation and HRAS mutation identified in pituitary spindle cell oncocytomaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalOncotargeten
dash.depositing.authorBi, Wenya Lindaen_US
dc.date.available2016-12-02T15:24:44Z
dc.identifier.doi10.18632/oncotarget.9244*
dash.authorsorderedfalse
dash.contributor.affiliatedAgarwalla, Pankaj Kumar
dash.contributor.affiliatedLaws, Edward
dash.contributor.affiliatedBi, Wenya
dash.contributor.affiliatedAlexander, Brian
dash.contributor.affiliatedLigon, Keith
dash.contributor.affiliatedReardon, David
dash.contributor.affiliatedWen, Patrick
dash.contributor.affiliatedDunn, Ian
dash.contributor.affiliatedBeroukhim, Rameen


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