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dc.contributor.authorMjøs, Siven_US
dc.contributor.authorWerner, Henrica Maria Johannaen_US
dc.contributor.authorBirkeland, Evenen_US
dc.contributor.authorHolst, Frederiken_US
dc.contributor.authorBerg, Annaen_US
dc.contributor.authorHalle, Mari Kyllesøen_US
dc.contributor.authorTangen, Ingvild Løbergen_US
dc.contributor.authorKusonmano, Kanthidaen_US
dc.contributor.authorMauland, Karen Klepslanden_US
dc.contributor.authorØyan, Anne Margreteen_US
dc.contributor.authorKalland, Karl-Henningen_US
dc.contributor.authorLewis, Aurelia Evaen_US
dc.contributor.authorMills, Gordon B.en_US
dc.contributor.authorKrakstad, Camillaen_US
dc.contributor.authorTrovik, Joneen_US
dc.contributor.authorSalvesen, Helgaen_US
dc.contributor.authorHøivik, Erling Andreen_US
dc.PublishedMjøs S, Werner HMJ, Birkeland E, Holst F, Berg A, Halle MK, Tangen IL, Kusonmano K, Mauland KK, Øyan AM, Kalland K-H, Lewis AE, Mills GB, Krakstad C, Trovik J, Salvesen H, Høivik EA. PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer. Scientific Reports. 2017;7:10240eng
dc.description.abstractMutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer.en_US
dc.publisherNature Publishing Groupeng
dc.rightsAttribution CC BYeng
dc.titlePIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial canceren_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2017 The Author(s)
dc.source.journalScientific Reports

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