An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

被引：47

作者：

Collord, Grace ^{[1
,2
]}

Tarpey, Patrick ^{[1
]}

Kurbatova, Natalja ^{[3
]}

Martincorena, Inigo ^{[1
]}

Moran, Sebastian ^{[4
]}

Castro, Manuel ^{[4
]}

Nagy, Tibor ^{[1
]}

Bignell, Graham ^{[1
]}

Maura, Francesco ^{[1
,5
,6
]}

Young, Matthew D. ^{[1
]}

Berna, Jorge ^{[7
]}

Tubio, Jose M. C. ^{[7
]}

McMurran, Chris E. ^{[8
]}

Young, Adam M. H. ^{[8
]}

Sanders, Mathijs ^{[1
,22
]}

Noorani, Imran ^{[1
,8
]}

Price, Stephen J. ^{[8
]}

Watts, Colin ^{[9
]}

Leipnitz, Elke ^{[10
]}

Kirsch, Matthias ^{[10
]}

Schackert, Gabriele ^{[10
]}

Pearson, Danita ^{[11
]}

Devadass, Abel ^{[11
]}

Ram, Zvi ^{[18
]}

Collins, V. Peter ^{[11
]}

Allinson, Kieren ^{[11
]}

Jenkinson, Michael D. ^{[12
,21
]}

Zakaria, Rasheed ^{[12
,13
]}

Syed, Khaja ^{[12
,13
]}

Hanemann, C. Oliver ^{[14
,15
]}

Dunn, Jemma ^{[14
,15
]}

McDermott, Michael W. ^{[16
]}

Kirollos, Ramez W. ^{[8
]}

Vassiliou, George S. ^{[1
,17
]}

Esteller, Manel ^{[4
,19
,20
]}

Behjati, Sam ^{[1
,2
]}

Brazma, Alvis ^{[3
]}

Santarius, Thomas ^{[8
]}

McDermott, Ultan ^{[1
,21
,23
]}

机构：

[1] Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton CB10 1SA, England

[2] Univ Cambridge, Dept Paediat, Cambridge Biomed Campus, Cambridge CB2 0QQ, England

[3] EBI, EMBL, Wellcome Trust Genome Campus, Hinxton CB10 1SD, England

[4] Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona, Catalonia, Spain

[5] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy

[6] Fdn IRCCS Ist Nazl Tumori, Dept Hematol, Milan, Italy

[7] Univ Santiago de Compostela, Mol Med & Chron Dis Ctr CIMUS, Mobile Genomes & Dis, Santiago De Compostela 15706, Spain

[8] Cambridge Univ Hosp NHS Fdn Trust, Dept Clin Neurosci, Dept Neurosurg, Cambridge CB2 0QQ, England

[9] Univ Birmingham, Inst Canc & Genom Sci, Dept Neurosurg, Birmingham, W Midlands, England

[10] Tech Univ Dresden, Carl Gustav Carus Univ Klinikum, Klin & Poliklink Neurochirurg, Fetscherstr 74, D-01307 Dresden, Germany

[11] Cambridge Univ Hosp, Dept Pathol, Cambridge CB2 0QQ, England

[12] Walton Ctr, Dept Neurosurg, Liverpool L9 7LJ, Merseyside, England

[13] Univ Liverpool, Inst Integrat Biol, Liverpool L9 7LJ, Merseyside, England

[14] Plymouth Univ, Peninsula Sch Med, Inst Translat & Stratified Med, Plymouth PL4 8AA, Devon, England

[15] Plymouth Univ, Peninsula Sch Dent, Inst Translat & Stratified Med, Plymouth PL4 8AA, Devon, England

[16] UCSF Med Ctr, Dept Neurosurg, San Francisco, CA 94143 USA

[17] Cambridge Univ Hosp NHS Trust, Dept Haematol, Cambridge CB2 0QQ, England

[18] Tel Aviv Med Ctr & Sch Med, Dept Neurosurg, Tel Aviv, Israel

[19] UB, Sch Med & Hlth Sci, Physiol Sci Dept, Catalonia, Spain

[20] ICREA, Barcelona, Catalonia, Spain

[21] Univ Liverpool, Inst Translat Med, Liverpool L9 7LJ, Merseyside, England

[22] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands

[23] AstraZeneca, CRUK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

英国惠康基金;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; NONCODING RNA HOTAIR; TUMOR-SUPPRESSOR; BREAST-CANCER; SOMATIC MUTATIONS; SWI/SNF COMPLEXES; TARGETING EZH2; GROWTH-FACTOR; HOX GENES; EXPRESSION;

D O I：

10.1038/s41598-018-31659-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.

引用

页数：13

共 117 条

[1] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[2] Differential expression analysis for sequence count data [J].

Anders, Simon ;

Huber, Wolfgang .

GENOME BIOLOGY, 2010, 11 (10)

[3] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[4]

[Anonymous], BIORXIV

[5] Knockdown of long non-coding RNA HOTAIR increases miR-454-3p by targeting Stat3 and Atg12 to inhibit chondrosarcoma growth [J].

Bao, Xing ;

Ren, Tingting ;

Huang, Yi ;

Sun, Kunkun ;

Wang, Shidong ;

Liu, Kuisheng ;

Zheng, Bingxin ;

Guo, Wei .

CELL DEATH & DISEASE, 2017, 8 :e2605-e2605

[6] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].

Ben-Porath, Ittai ;

Thomson, Matthew W. ;

Carey, Vincent J. ;

Ge, Ruping ;

Bell, George W. ;

Regev, Aviv ;

Weinberg, Robert A. .

NATURE GENETICS, 2008, 40 (05) :499-507

[7] CXCL14: the Swiss army knife chemokine [J].

Benarafa, Charaf ;

Wolf, Marlene .

ONCOTARGET, 2015, 6 (33) :34065-34066

[8] Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer [J].

Bernhart, Stephan H. ;

Kretzmer, Helene ;

Holdt, Lesca M. ;

Juehling, Frank ;

Ammerpohl, Ole ;

Bergmann, Anke K. ;

Northoff, Bernd H. ;

Doose, Gero ;

Siebert, Reiner ;

Stadler, Peter F. ;

Hoffmann, Steve .

SCIENTIFIC REPORTS, 2016, 6

[9] A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].

Bernstein, BE ;

Mikkelsen, TS ;

Xie, XH ;

Kamal, M ;

Huebert, DJ ;

Cuff, J ;

Fry, B ;

Meissner, A ;

Wernig, M ;

Plath, K ;

Jaenisch, R ;

Wagschal, A ;

Feil, R ;

Schreiber, SL ;

Lander, ES .

CELL, 2006, 125 (02) :315-326

[10] Involvement of Members of the Cadherin Superfamily in Cancer [J].

Berx, Geert ;

van Roy, Frans .

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2009, 1 (06) :a003129

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