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Macrophage infiltration and genetic landscape of undifferentiated uterine sarcomas

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dc.abstract.enEndometrial stromal tumors include translocation-associated low- and high-grade endometrial stromal sarcomas (ESS) and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of aggressive tumors and is often seen as a diagnosis of exclusion after ESS and leiomyosarcoma (LMS) have been ruled out. We performed a comprehensive analysis of gene expression, copy number variation, point mutations, and immune cell infiltrates in the largest series to date of all major types of uterine sarcomas to shed light on the biology of UUS and to identify potential novel therapeutic targets. We show that UUS tumors have a distinct molecular profile from LMS and ESS. Gene expression and immunohistochemical analyses revealed the presence of high numbers of tumor-associated macrophages (TAMs) in UUS, which makes UUS patients suitable candidates for therapies targeting TAMs. Our results show a high genomic instability of UUS and downregulation of several TP53-mediated tumor suppressor genes, such as NDN, CDH11, and NDRG4. Moreover, we demonstrate that UUS carry somatic mutations in several oncogenes and tumor suppressor genes implicated in RAS/PI3K/AKT/mTOR, ERBB3, and Hedgehog signaling.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorVarma, Sushama
dc.contributor.authorVanspauwen, Vanessa
dc.contributor.authorNewman, Aaron
dc.contributor.authorVennam, Sujay
dc.contributor.authorDewaele, Barbara
dc.contributor.authorQuattrone, Anna
dc.contributor.authorPrzybył, Joanna
dc.contributor.authorRijn, Matt Van De
dc.contributor.authorCools, Jan
dc.contributor.authorBakuła-Zalewska, Elwira
dc.contributor.authorŚwierniak, Michał
dc.contributor.authorSiedlecki, Janusz
dc.contributor.authorKowalewska, Magdalena
dc.contributor.authorDebiec-Rychter, Maria
dc.contributor.authorBidziński, Mariusz
dc.date.accessioned2024-01-25T05:30:34Z
dc.date.available2024-01-25T05:30:34Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.identifier.doi10.1172/JCI.INSIGHT.94033
dc.identifier.issn0021-9738
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/111644
dc.languageeng
dc.pbn.affiliationmedical sciences
dc.relation.ispartofJournal of Clinical Investigation
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleMacrophage infiltration and genetic landscape of undifferentiated uterine sarcomas
dc.typeJournalArticle
dspace.entity.typePublication