000170013 001__ 170013
000170013 005__ 20240229133703.0
000170013 0247_ $$2doi$$a10.1038/s41379-021-00874-y
000170013 0247_ $$2pmid$$apmid:34312479
000170013 0247_ $$2ISSN$$a0893-3952
000170013 0247_ $$2ISSN$$a1530-0285
000170013 0247_ $$2altmetric$$aaltmetric:110469108
000170013 037__ $$aDKFZ-2021-01707
000170013 041__ $$aEnglish
000170013 082__ $$a610
000170013 1001_ $$00000-0001-8763-8864$$aKoelsche, Christian$$b0
000170013 245__ $$aIntimal sarcomas and undifferentiated cardiac sarcomas carry mutually exclusive MDM2, MDM4, and CDK6 amplifications and share a common DNA methylation signature.
000170013 260__ $$aLondon$$bNature Publishing Group$$c2021
000170013 3367_ $$2DRIVER$$aarticle
000170013 3367_ $$2DataCite$$aOutput Types/Journal article
000170013 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1642171817_16251
000170013 3367_ $$2BibTeX$$aARTICLE
000170013 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000170013 3367_ $$00$$2EndNote$$aJournal Article
000170013 500__ $$a#LA:B300# / 2021 Dec;34(12):2122-2129
000170013 520__ $$aUndifferentiated mesenchymal tumors arising from the inner lining (intima) of large arteries are classified as intimal sarcomas (ISA) with MDM2 amplification as their molecular hallmark. Interestingly, undifferentiated pleomorphic sarcomas (UPS) of the heart have recently been suggested to represent the cardiac analog of ISA due to morphological overlap and high prevalence of MDM2 amplifications in both neoplasms. However, little is known about ISAs and cardiac UPS without MDM2 amplifications and molecular data supporting their common classification is sparse. Here, we report a series of 35 cases comprising 25 ISAs of the pulmonary artery, one ISA of the renal artery and 9 UPS of the left atrium. Tumors were analyzed utilizing the Illumina Infinium MethylationEPIC BeadChip array, enabling copy number profile generation and unsupervised DNA methylation analysis. DNA methylation patterns were investigated using t-distributed stochastic neighbor embedding (t-SNE) analysis. Histologically, all ISAs and UPS of the left atrium resembled extra-cardiac UPS. All cases exhibited highly complex karyotypes with overlapping patterns between ISA and UPS. 29/35 cases showed mutually exclusive amplifications in the cell-cycle associated oncogenes MDM2 (25/35), MDM4 (2/35), and CDK6 (2/35). We further observed recurrent co-amplifications in PDGFRA (21/35), CDK4 (15/35), TERT (11/35), HDAC9 (9/35), and CCND1 (4/35). Sporadic co-amplifications occurred in MYC, MYCN, and MET (each 1/35). The tumor suppressor CDKN2A/B was frequently deleted (10/35). Interestingly, DNA methylation profiling (t-SNE) revealed an overlap of ISA and cardiac UPS. This 'ISA' methylation signature was distinct from potential histologic and molecular mimics. In conclusion, our data reveal MDM4 and CDK6 amplifications in ISAs and UPS of the left atrium, lacking MDM2 amplification. We further report novel co-amplifications of various oncogenes, which may have therapeutic implications. Finally, the genetic and epigenetic concordance of ISAs and UPS of the left atrium further supports a shared pathogenesis and common classification.
000170013 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0
000170013 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de
000170013 7001_ $$00000-0001-5542-9857$$aBenhamida, Jamal K$$b1
000170013 7001_ $$aKommoss, Felix K F$$b2
000170013 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b3$$udkfz
000170013 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b4$$udkfz
000170013 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b5$$udkfz
000170013 7001_ $$0P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aHeilig, Christoph E$$b6$$udkfz
000170013 7001_ $$0P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aFröhling, Stefan$$b7$$udkfz
000170013 7001_ $$aStenzinger, Albrecht$$b8
000170013 7001_ $$00000-0002-1490-8867$$aBuslei, Rolf$$b9
000170013 7001_ $$aMentzel, Thomas$$b10
000170013 7001_ $$00000-0002-2137-7507$$aBaumhoer, Daniel$$b11
000170013 7001_ $$aLadanyi, Marc$$b12
000170013 7001_ $$00000-0002-9717-8205$$aAntonescu, Cristina R$$b13
000170013 7001_ $$aFlucke, Uta$$b14
000170013 7001_ $$aGorp, Joost van$$b15
000170013 7001_ $$00000-0002-3329-4186$$aBode-Lesniewska, Beata$$b16
000170013 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b17$$eLast author$$udkfz
000170013 7001_ $$aMechtersheimer, Gunhild$$b18
000170013 773__ $$0PERI:(DE-600)2041318-X$$a10.1038/s41379-021-00874-y$$n12$$p2122-2129$$tModern pathology$$v34$$x1530-0285$$y2021
000170013 909CO $$ooai:inrepo02.dkfz.de:170013$$pVDB
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000170013 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$aDeutsches Krebsforschungszentrum$$b17$$kDKFZ
000170013 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0
000170013 9141_ $$y2021
000170013 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bMODERN PATHOL : 2019$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2021-01-28
000170013 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bMODERN PATHOL : 2019$$d2021-01-28
000170013 9201_ $$0I:(DE-He78)B300-20160331$$kB300$$lKKE Neuropathologie$$x0
000170013 9201_ $$0I:(DE-He78)HD01-20160331$$kHD01$$lDKTK HD zentral$$x1
000170013 9201_ $$0I:(DE-He78)B360-20160331$$kB360$$lPediatric Glioma$$x2
000170013 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x3
000170013 9201_ $$0I:(DE-He78)B340-20160331$$kB340$$lTranslationale Medizinische Onkologie$$x4
000170013 980__ $$ajournal
000170013 980__ $$aVDB
000170013 980__ $$aI:(DE-He78)B300-20160331
000170013 980__ $$aI:(DE-He78)HD01-20160331
000170013 980__ $$aI:(DE-He78)B360-20160331
000170013 980__ $$aI:(DE-He78)B062-20160331
000170013 980__ $$aI:(DE-He78)B340-20160331
000170013 980__ $$aUNRESTRICTED