Robust diagnosis of ewing sarcoma by immunohistochemical detection of super-enhancer-drivenewsr1-ets targets

Basit Öğe Kaydı
dc.contributor.authorAkpolat, Nusret
dc.contributor.authorAkatli, Ayse N.
dc.date.accessioned2019-07-19T10:21:23Z
dc.date.available2019-07-19T10:21:23Z
dc.date.issued2018
dc.departmentİnönü Üniversitesien_US
dc.description.abstractEwing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B-and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care.en_US
dc.identifier.citationAkpolat, N. Akatli, AN. (2018). Robust diagnosis of ewing sarcoma by immunohistochemical detection of super-enhancer-drivenewsr1-ets targets. Cilt:9. Sayı:2. 1587-1601 ss.en_US
dc.identifier.doi10.18632/oncotarget.20098en_US
dc.identifier.endpage1601en_US
dc.identifier.issue2en_US
dc.identifier.startpage1587en_US
dc.identifier.urihttps://hdl.handle.net/11616/12787
dc.identifier.volume9en_US
dc.language.isoenen_US
dc.publisherImpact journals llc, 6666 e quaker st, ste 1, orchard park, ny 14127 usaen_US
dc.relation.ispartofOncotargeten_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectRound-cell sarcomasen_US
dc.subjecttranscrıptıon factorsen_US
dc.subjectsoft-tıssueen_US
dc.subjectexpressıonen_US
dc.subjecttumorsen_US
dc.subjectgeneen_US
dc.subjectfusıonen_US
dc.subjectfamılyen_US
dc.subjectewsr1-flı1en_US
dc.subjectchromatınen_US
dc.titleRobust diagnosis of ewing sarcoma by immunohistochemical detection of super-enhancer-drivenewsr1-ets targetsen_US
dc.typeArticleen_US

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
makale.pdf
Boyut:
9.4 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Makale dosyası
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.71 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Koleksiyonu