Intimal sarcomas and undifferentiated cardiac sarcomas carry mutually exclusive MDM2, MDM4, and CDK6 amplifications and share a common DNA methylation signature
Undifferentiated 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...
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| Published in | Modern pathology Vol. 34; no. 12; pp. 2122 - 2129 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.12.2021
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0893-3952 1530-0285 1530-0285 |
| DOI | 10.1038/s41379-021-00874-y |
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| Abstract | Undifferentiated 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. |
|---|---|
| AbstractList | Undifferentiated 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. Undifferentiated 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. Undifferentiated 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.Undifferentiated 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. |
| Author | Stenzinger, Albrecht Kommoss, Felix K. F. Baumhoer, Daniel Jones, David T. W. Pfister, Stefan M. Ladanyi, Marc Buslei, Rolf Stichel, Damian Fröhling, Stefan Flucke, Uta Antonescu, Cristina R. Koelsche, Christian Benhamida, Jamal K. Heilig, Christoph E. Bode-Lesniewska, Beata Gorp, Joost van Deimling, Andreas von Mechtersheimer, Gunhild Mentzel, Thomas |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34312479$$D View this record in MEDLINE/PubMed |
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| PublicationSubtitle | Publishing innovative clinical and translational research in the pathology of human disease |
| PublicationTitle | Modern pathology |
| PublicationTitleAbbrev | Mod Pathol |
| PublicationTitleAlternate | Mod Pathol |
| PublicationYear | 2021 |
| Publisher | Nature Publishing Group US Elsevier Limited |
| Publisher_xml | – name: Nature Publishing Group US – name: Elsevier Limited |
| References | StaatsPTavoraFBurkeAPIntimal sarcomas of the aorta and iliofemoral arteries: a clinicopathological study of 26 casesPathology2014465966031:CAS:528:DC%2BC2cXhvFGgu7fM10.1097/PAT.0000000000000182 CapperDJonesDTWSillMHovestadtVSchrimpfDSturmDDNA methylation-based classification of central nervous system tumoursNature2018555469741:CAS:528:DC%2BC1cXksFegu70%3D10.1038/nature26000 ZhangHMacdonaldWDErickson-JohnsonMWangXJenkinsRBOliveiraAMCytogenetic and molecular cytogenetic findings of intimal sarcomaCancer Genet Cytogenet20071791461491:CAS:528:DC%2BD2sXhtlCrs7fL10.1016/j.cancergencyto.2007.08.013 Van DievelJSciotRDelcroixMVandeweyerRODebiec-RychterMDewaeleBSingle-center experience with intimal sarcoma, an ultra-orphan, commonly fatal mesenchymal malignancyOncol Res Treat20174035335910.1159/000476036 KommossFKFStichelDSchrimpfDKriegsmannMTessier-CloutierBTalhoukADNA methylation-based profiling of uterine neoplasms: a novel tool to improve gynecologic cancer diagnosticsJ Cancer Res Clin Oncol2020146971041:CAS:528:DC%2BC1MXitlOmsb7F10.1007/s00432-019-03093-w CapperDStichelDSahmFJonesDTWSchrimpfDSillMPractical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experienceActa Neuropathol20181361812101:CAS:528:DC%2BC1cXht1yks7vL10.1007/s00401-018-1879-y BasturkOWeigeltBAdsayVBenhamidaJKAskanGWangLSclerosing epithelioid mesenchymal neoplasm of the pancreas - a proposed new entityMod Pathol202033456671:CAS:528:DC%2BC1MXhsFCmsr%2FE10.1038/s41379-019-0334-5 Bode-LesniewskaBZhaoJSpeelEJBiraimaAMTurinaMKomminothPGains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary arteryVirchows Arch200143857651:CAS:528:DC%2BD3MXlt1Oisw%3D%3D10.1007/s004280000313 MaleszewskiJJTavoraFBurkeAPDo “intimal” sarcomas of the heart exist?Am J Surg Pathol2014381158115910.1097/PAS.0000000000000271 RohrichMKoelscheCSchrimpfDCapperDSahmFKratzAMethylation-based classification of benign and malignant peripheral nerve sheath tumorsActa Neuropathol20161318778710.1007/s00401-016-1540-6 Cancer Genome Atlas Research Network. Electronic address, e. d. s. c. & Cancer Genome Atlas Research, N. Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. Cell. 2017;171:950–965 e928. WHO Classification of Tumours of Soft Tissue and Bone. 5th edn, Vol. 3 (2020). NeuvilleACoindreJMCardiac sarcoma with MDM2 amplificationAm J Surg Pathol201438144910.1097/PAS.0000000000000275 TaylorBSBarretinaJMakiRGAntonescuCRSingerSLadanyiMAdvances in sarcoma genomics and new therapeutic targetsNat Rev Cancer201111541571:CAS:528:DC%2BC3MXovFehur4%3D10.1038/nrc3087 FrezzaAMAssiTLo VulloSBen-AmiEDufresneAYonemoriKSystemic treatments in MDM2 positive intimal sarcoma: a multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma NetworkCancer2020126981041:CAS:528:DC%2BB3cXls1KitA%3D%3D10.1002/cncr.32508 CoindreJMHosteinIMaireGDerreJGuillouLLerouxAInflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entityJ Pathol2004203822301:CAS:528:DC%2BD2cXmtFSmtLs%3D10.1002/path.1579 HottenrottGMentzelTPetersASchroderAKatenkampDIntravascular (“intimal”) epithelioid angiosarcoma: clinicopathological and immunohistochemical analysis of three casesVirchows Arch19994354734781:STN:280:DC%2BD3c%2FmtVSiuw%3D%3D10.1007/s004280050430 Mandelstamm, M. Über primäre Neubildungen des Herzens. Virchows Arch. 1923:43–54. WeidemaMEvan de GeerEKoelscheCDesarIMEKemmerenPHillebrandt-RoeffenMHSDNA methylation profiling identifies distinct clusters in angiosarcomasClin Cancer Res202026931001:CAS:528:DC%2BB3cXhslGns7zE10.1158/1078-0432.CCR-19-2180 HauptSMejia-HernandezJOVijayakumaranRKeamSPHauptYThe long and the short of it: the MDM4 tail so farJ Mol Cell Biol201911231441:CAS:528:DC%2BB3cXjslCls7o%3D10.1093/jmcb/mjz007 CoindreJMMarianiOChibonFMairalADe Saint Aubain SomerhausenNFavre-GuillevinEMost malignant fibrous histiocytomas developed in the retroperitoneum are dedifferentiated liposarcomas: a review of 25 cases initially diagnosed as malignant fibrous histiocytomaMod Pathol2003162566210.1097/01.MP.0000056983.78547.77 KoelscheCStichelDGriewankKGSchrimpfDReussDEBewerunge-HudlerMGenome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotypeClin Sarcoma Res2019910.1186/s13569-019-0113-6 DewaeleBFlorisGFinalet-FerreiroJFletcherCDCoindreJMGuillouLCoactivated platelet-derived growth factor receptor {alpha} and epidermal growth factor receptor are potential therapeutic targets in intimal sarcomaCancer Res2010707304141:CAS:528:DC%2BC3cXhtFGqtrjL10.1158/0008-5472.CAN-10-1543 TavoraFMiettinenMFanburg-SmithJFranksTJBurkeAPulmonary artery sarcoma: a histologic and follow-up study with emphasis on a subset of low-grade myofibroblastic sarcomas with a good long-term follow-upAm J Surg Pathol20083217516110.1097/PAS.0b013e31817d7fd0 BurkeAPVirmaniRSarcomas of the great vessels. A clinicopathologic studyCancer1993711761731:STN:280:DyaK3s7ptlSltQ%3D%3D10.1002/1097-0142(19930301)71:5<1761::AID-CNCR2820710510>3.0.CO;2-7 MildeTOehmeIKorshunovAKopp-SchneiderARemkeMNorthcottPHDAC5 and HDAC9 in medulloblastoma: novel markers for risk stratification and role in tumor cell growthClin Cancer Res2010163240521:CAS:528:DC%2BC3cXntlKqsr0%3D10.1158/1078-0432.CCR-10-0395 KoelscheCHartmannWSchrimpfDStichelDJabarSRanftAArray-based DNA-methylation profiling in sarcomas with small blue round cell histology provides valuable diagnostic informationMod Pathol2018311246561:CAS:528:DC%2BC1cXht1CgtLjJ10.1038/s41379-018-0045-3 WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn, Vol. 7 (2015). Ten BroekRWKoelscheCEijkelenboomAMentzelTCreytensDVokuhlCKaposiform hemangioendothelioma and tufted angioma - (epi)genetic analysis including genome-wide methylation profilingAnn Diagn Pathol20204415143410.1016/j.anndiagpath.2019.151434 ItoYMaedaDYoshidaMYoshidaAKudo-AsabeYNanjyoHCardiac intimal sarcoma with PDGFRbeta mutation and co-amplification of PDGFRalpha and MDM2: an autopsy case analyzed by whole-exome sequencingVirchows Arch201747142342810.1007/s00428-017-2135-x BurkeATavoraFThe 2015 WHO Classification of Tumors of the Heart and PericardiumJ Thorac Oncol2016114415210.1016/j.jtho.2015.11.009 BarretinaJTaylorBSBanerjiSRamosAHLagos-QuintanaMDecarolisPLSubtype-specific genomic alterations define new targets for soft-tissue sarcoma therapyNat Genet201042715211:CAS:528:DC%2BC3cXotlWktLY%3D10.1038/ng.619 Le GuellecSChibonFOualiMPerotGDecouvelaereAVRobinYMAre peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?Am J Surg Pathol20143829330410.1097/PAS.0000000000000131 Watson, R, Frye, J, Trieu, M & Yang, MX Primary undifferentiated pleomorphic cardiac sarcoma with MDM2 amplification presenting as acute left-sided heart failure. BMJ Case Rep2018 (2018). KoelscheCSchrimpfDStichelDSillMSahmFReussDESarcoma classification by DNA methylation profilingNat Commun2021121:CAS:528:DC%2BB3MXhvF2jsro%3D10.1038/s41467-020-20603-4 SebenikMRicciAJr.DiPasqualeBModyKPytelPJeeKJUndifferentiated intimal sarcoma of large systemic blood vessels: report of 14 cases with immunohistochemical profile and review of the literatureAm J Surg Pathol20052911849310.1097/01.pas.0000159774.70288.7d PajtlerKWWittHSillMJonesDTHovestadtVKratochwilFMolecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groupsCancer Cell201527728431:CAS:528:DC%2BC2MXosVamurY%3D10.1016/j.ccell.2015.04.002 ZhaoJRothJBode-LesniewskaBPfaltzMHeitzPUKomminothPCombined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumorsGenes Chromosomes Cancer20023448571:CAS:528:DC%2BD38XjtFWju7o%3D10.1002/gcc.10035 NebenfuehrSKollmannKSexlVThe role of CDK6 in cancerInt J Cancer20201472988951:CAS:528:DC%2BB3cXhtFWksrrM10.1002/ijc.33054 YuanXLarssonCXuDMechanisms underlying the activation of TERT transcription and telomerase activity in human cancer: old actors and new playersOncogene2019386172831:CAS:528:DC%2BC1MXhtlertr7M10.1038/s41388-019-0872-9 NeuvilleACollinFBrunevalPParrensMThivoletFGomez-BrouchetAIntimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomasAm J Surg Pathol20143846146910.1097/PAS.0000000000000184 KoelscheCMynarekMSchrimpfDBerteroLSerranoJSahmFPrimary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutationsActa Neuropathol2018136327371:CAS:528:DC%2BC1cXhtFGgsLbI10.1007/s00401-018-1871-6 Roszik, J, Khan, A, Conley, AP, Livingston, JA, Groisberg, R, Ravi, V et al. Unique aberrations in intimal sarcoma identified by next-generation sequencing as potential therapy targets. Cancers (Basel). 2019:11. HovestadtVRemkeMKoolMPietschTNorthcottPAFischerRRobust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arraysActa Neuropathol201312591391610.1007/s00401-013-1126-5 FittallMWLyskjaerIElleryPLombardPIjazJStroblACDrivers underpinning the malignant transformation of giant cell tumour of boneJ Pathol2020252433401:CAS:528:DC%2BB3cXis1ShsrzO10.1002/path.5537 Staats (10.1038/s41379-021-00874-y_bib5) 2014; 46 Ten Broek (10.1038/s41379-021-00874-y_bib25) 2020; 44 Milde (10.1038/s41379-021-00874-y_bib36) 2010; 16 Kommoss (10.1038/s41379-021-00874-y_bib27) 2020; 146 Koelsche (10.1038/s41379-021-00874-y_bib28) 2018; 31 10.1038/s41379-021-00874-y_bib3 Capper (10.1038/s41379-021-00874-y_bib31) 2018; 136 Coindre (10.1038/s41379-021-00874-y_bib41) 2003; 16 Sebenik (10.1038/s41379-021-00874-y_bib10) 2005; 29 Neuville (10.1038/s41379-021-00874-y_bib13) 2014; 38 Bode-Lesniewska (10.1038/s41379-021-00874-y_bib9) 2001; 438 10.1038/s41379-021-00874-y_bib15 Koelsche (10.1038/s41379-021-00874-y_bib44) 2019; 9 Haupt (10.1038/s41379-021-00874-y_bib34) 2019; 11 10.1038/s41379-021-00874-y_bib32 Van Dievel (10.1038/s41379-021-00874-y_bib39) 2017; 40 Ito (10.1038/s41379-021-00874-y_bib14) 2017; 471 Hovestadt (10.1038/s41379-021-00874-y_bib30) 2013; 125 Maleszewski (10.1038/s41379-021-00874-y_bib17) 2014; 38 Barretina (10.1038/s41379-021-00874-y_bib38) 2010; 42 10.1038/s41379-021-00874-y_bib19 Burke (10.1038/s41379-021-00874-y_bib6) 1993; 71 Nebenfuehr (10.1038/s41379-021-00874-y_bib33) 2020; 147 Fittall (10.1038/s41379-021-00874-y_bib29) 2020; 252 Burke (10.1038/s41379-021-00874-y_bib18) 2016; 11 Weidema (10.1038/s41379-021-00874-y_bib24) 2020; 26 Basturk (10.1038/s41379-021-00874-y_bib43) 2020; 33 Frezza (10.1038/s41379-021-00874-y_bib2) 2020; 126 Neuville (10.1038/s41379-021-00874-y_bib16) 2014; 38 Zhao (10.1038/s41379-021-00874-y_bib8) 2002; 34 Yuan (10.1038/s41379-021-00874-y_bib35) 2019; 38 Coindre (10.1038/s41379-021-00874-y_bib42) 2004; 203 Koelsche (10.1038/s41379-021-00874-y_bib22) 2021; 12 Koelsche (10.1038/s41379-021-00874-y_bib23) 2018; 136 Hottenrott (10.1038/s41379-021-00874-y_bib4) 1999; 435 Rohrich (10.1038/s41379-021-00874-y_bib26) 2016; 131 Capper (10.1038/s41379-021-00874-y_bib21) 2018; 555 Pajtler (10.1038/s41379-021-00874-y_bib45) 2015; 27 10.1038/s41379-021-00874-y_bib1 10.1038/s41379-021-00874-y_bib20 Dewaele (10.1038/s41379-021-00874-y_bib12) 2010; 70 Zhang (10.1038/s41379-021-00874-y_bib11) 2007; 179 Taylor (10.1038/s41379-021-00874-y_bib37) 2011; 11 Tavora (10.1038/s41379-021-00874-y_bib7) 2008; 32 Le Guellec (10.1038/s41379-021-00874-y_bib40) 2014; 38 |
| References_xml | – reference: FittallMWLyskjaerIElleryPLombardPIjazJStroblACDrivers underpinning the malignant transformation of giant cell tumour of boneJ Pathol2020252433401:CAS:528:DC%2BB3cXis1ShsrzO10.1002/path.5537 – reference: TavoraFMiettinenMFanburg-SmithJFranksTJBurkeAPulmonary artery sarcoma: a histologic and follow-up study with emphasis on a subset of low-grade myofibroblastic sarcomas with a good long-term follow-upAm J Surg Pathol20083217516110.1097/PAS.0b013e31817d7fd0 – reference: PajtlerKWWittHSillMJonesDTHovestadtVKratochwilFMolecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groupsCancer Cell201527728431:CAS:528:DC%2BC2MXosVamurY%3D10.1016/j.ccell.2015.04.002 – reference: KoelscheCSchrimpfDStichelDSillMSahmFReussDESarcoma classification by DNA methylation profilingNat Commun2021121:CAS:528:DC%2BB3MXhvF2jsro%3D10.1038/s41467-020-20603-4 – reference: HauptSMejia-HernandezJOVijayakumaranRKeamSPHauptYThe long and the short of it: the MDM4 tail so farJ Mol Cell Biol201911231441:CAS:528:DC%2BB3cXjslCls7o%3D10.1093/jmcb/mjz007 – reference: HovestadtVRemkeMKoolMPietschTNorthcottPAFischerRRobust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arraysActa Neuropathol201312591391610.1007/s00401-013-1126-5 – reference: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn, Vol. 7 (2015). – reference: CoindreJMHosteinIMaireGDerreJGuillouLLerouxAInflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entityJ Pathol2004203822301:CAS:528:DC%2BD2cXmtFSmtLs%3D10.1002/path.1579 – reference: BasturkOWeigeltBAdsayVBenhamidaJKAskanGWangLSclerosing epithelioid mesenchymal neoplasm of the pancreas - a proposed new entityMod Pathol202033456671:CAS:528:DC%2BC1MXhsFCmsr%2FE10.1038/s41379-019-0334-5 – reference: KommossFKFStichelDSchrimpfDKriegsmannMTessier-CloutierBTalhoukADNA methylation-based profiling of uterine neoplasms: a novel tool to improve gynecologic cancer diagnosticsJ Cancer Res Clin Oncol2020146971041:CAS:528:DC%2BC1MXitlOmsb7F10.1007/s00432-019-03093-w – reference: NeuvilleACollinFBrunevalPParrensMThivoletFGomez-BrouchetAIntimal sarcoma is the most frequent primary cardiac sarcoma: clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomasAm J Surg Pathol20143846146910.1097/PAS.0000000000000184 – reference: DewaeleBFlorisGFinalet-FerreiroJFletcherCDCoindreJMGuillouLCoactivated platelet-derived growth factor receptor {alpha} and epidermal growth factor receptor are potential therapeutic targets in intimal sarcomaCancer Res2010707304141:CAS:528:DC%2BC3cXhtFGqtrjL10.1158/0008-5472.CAN-10-1543 – reference: BurkeAPVirmaniRSarcomas of the great vessels. A clinicopathologic studyCancer1993711761731:STN:280:DyaK3s7ptlSltQ%3D%3D10.1002/1097-0142(19930301)71:5<1761::AID-CNCR2820710510>3.0.CO;2-7 – reference: WeidemaMEvan de GeerEKoelscheCDesarIMEKemmerenPHillebrandt-RoeffenMHSDNA methylation profiling identifies distinct clusters in angiosarcomasClin Cancer Res202026931001:CAS:528:DC%2BB3cXhslGns7zE10.1158/1078-0432.CCR-19-2180 – reference: MildeTOehmeIKorshunovAKopp-SchneiderARemkeMNorthcottPHDAC5 and HDAC9 in medulloblastoma: novel markers for risk stratification and role in tumor cell growthClin Cancer Res2010163240521:CAS:528:DC%2BC3cXntlKqsr0%3D10.1158/1078-0432.CCR-10-0395 – reference: Watson, R, Frye, J, Trieu, M & Yang, MX Primary undifferentiated pleomorphic cardiac sarcoma with MDM2 amplification presenting as acute left-sided heart failure. BMJ Case Rep2018 (2018). – reference: CapperDJonesDTWSillMHovestadtVSchrimpfDSturmDDNA methylation-based classification of central nervous system tumoursNature2018555469741:CAS:528:DC%2BC1cXksFegu70%3D10.1038/nature26000 – reference: TaylorBSBarretinaJMakiRGAntonescuCRSingerSLadanyiMAdvances in sarcoma genomics and new therapeutic targetsNat Rev Cancer201111541571:CAS:528:DC%2BC3MXovFehur4%3D10.1038/nrc3087 – reference: CoindreJMMarianiOChibonFMairalADe Saint Aubain SomerhausenNFavre-GuillevinEMost malignant fibrous histiocytomas developed in the retroperitoneum are dedifferentiated liposarcomas: a review of 25 cases initially diagnosed as malignant fibrous histiocytomaMod Pathol2003162566210.1097/01.MP.0000056983.78547.77 – reference: BurkeATavoraFThe 2015 WHO Classification of Tumors of the Heart and PericardiumJ Thorac Oncol2016114415210.1016/j.jtho.2015.11.009 – reference: Le GuellecSChibonFOualiMPerotGDecouvelaereAVRobinYMAre peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?Am J Surg Pathol20143829330410.1097/PAS.0000000000000131 – reference: BarretinaJTaylorBSBanerjiSRamosAHLagos-QuintanaMDecarolisPLSubtype-specific genomic alterations define new targets for soft-tissue sarcoma therapyNat Genet201042715211:CAS:528:DC%2BC3cXotlWktLY%3D10.1038/ng.619 – reference: ZhangHMacdonaldWDErickson-JohnsonMWangXJenkinsRBOliveiraAMCytogenetic and molecular cytogenetic findings of intimal sarcomaCancer Genet Cytogenet20071791461491:CAS:528:DC%2BD2sXhtlCrs7fL10.1016/j.cancergencyto.2007.08.013 – reference: ItoYMaedaDYoshidaMYoshidaAKudo-AsabeYNanjyoHCardiac intimal sarcoma with PDGFRbeta mutation and co-amplification of PDGFRalpha and MDM2: an autopsy case analyzed by whole-exome sequencingVirchows Arch201747142342810.1007/s00428-017-2135-x – reference: CapperDStichelDSahmFJonesDTWSchrimpfDSillMPractical implementation of DNA methylation and copy-number-based CNS tumor diagnostics: the Heidelberg experienceActa Neuropathol20181361812101:CAS:528:DC%2BC1cXht1yks7vL10.1007/s00401-018-1879-y – reference: StaatsPTavoraFBurkeAPIntimal sarcomas of the aorta and iliofemoral arteries: a clinicopathological study of 26 casesPathology2014465966031:CAS:528:DC%2BC2cXhvFGgu7fM10.1097/PAT.0000000000000182 – reference: Ten BroekRWKoelscheCEijkelenboomAMentzelTCreytensDVokuhlCKaposiform hemangioendothelioma and tufted angioma - (epi)genetic analysis including genome-wide methylation profilingAnn Diagn Pathol20204415143410.1016/j.anndiagpath.2019.151434 – reference: KoelscheCStichelDGriewankKGSchrimpfDReussDEBewerunge-HudlerMGenome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotypeClin Sarcoma Res2019910.1186/s13569-019-0113-6 – reference: Cancer Genome Atlas Research Network. Electronic address, e. d. s. c. & Cancer Genome Atlas Research, N. Comprehensive and integrated genomic characterization of adult soft tissue sarcomas. 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| Snippet | Undifferentiated mesenchymal tumors arising from the inner lining (intima) of large arteries are classified as intimal sarcomas (ISA) with
MDM2
amplification... Undifferentiated mesenchymal tumors arising from the inner lining (intima) of large arteries are classified as intimal sarcomas (ISA) with MDM2 amplification... |
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| Title | Intimal sarcomas and undifferentiated cardiac sarcomas carry mutually exclusive MDM2, MDM4, and CDK6 amplifications and share a common DNA methylation signature |
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