YAP1-FAM118B Fusion Defines a Rare Subset of Childhood and Young Adulthood Meningiomas.
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
pubmed:
20
10
2020
medline:
31
3
2021
entrez:
19
10
2020
Statut:
ppublish
Résumé
Meningiomas are a central nervous system tumor primarily afflicting adults, with <1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2 may be found in ∼50% of meningiomas, with other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to NF2 wild-type tumors. NF2 is an upstream negative regulator of YAP signaling and loss of the NF2 protein product, Merlin, results in YAP overexpression and target gene transcription. This mechanism of dysregulation is described in NF2-driven meningiomas, but further work is necessary to understand the NF2-independent mechanism of tumorigenesis. Amid our institutional patient-centric comprehensive molecular profiling study, we identified an individual with meningioma harboring a YAP1-FAM118B fusion, previously reported only in supratentorial ependymoma. The tumor histopathology was remarkable, characterized by prominent islands of calcifying fibrous nodules within an overall collagen-rich matrix. To gain insight into this finding, we subsequently evaluated the genetic landscape of 11 additional pediatric and adolescent/young adulthood meningioma patients within the Children's Brain Tumor Tissue Consortium. A second individual harboring a YAP1-FAM118B gene fusion was identified within this database. Transcriptomic profiling suggested that YAP1-fusion meningiomas are biologically distinct from NF2-driven meningiomas. Similar to other meningiomas, however, YAP1-fusion meningiomas demonstrated overexpression of EGFR and MET. DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2 wild-type meningioma to include the YAP1-FAM118B fusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.
Identifiants
pubmed: 33074854
pii: 00000478-202103000-00004
doi: 10.1097/PAS.0000000000001597
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
329-340Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The Nationwide Foundation Pediatric Innovation Fund provided funding for sequencing, data production, and analysis. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Références
Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99:307–314.
Dudley RWR, Torok MR, Randall S, et al. Pediatric versus adult meningioma: comparison of epidemiology, treatments, and outcomes using the Surveillance, Epidemiology, and End Results database. J Neurooncol. 2018;137:621–629.
Kotecha RS, Pascoe EM, Rushing EJ, et al. Meningiomas in children and adolescents: a meta-analysis of individual patient data. Lancet Oncol. 2011;12:1229–1239.
Goutagny S, Kalamarides M. Meningiomas and neurofibromatosis. J Neurooncol. 2010;99:341–347.
Brastianos PK, Horowitz PM, Santagata S, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45:285–289.
Harmancl AS, Youngblood MW, Clark VE, et al. Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nat Commun. 2017;8:14433.
Petrilli AM, Fernández-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35:537–548.
Zanconato F, Cordenonsi M, Piccolo S. YAP/TAZ at the roots of cancer. Cancer Cell. 2016;29:783–803.
Baia GS, Caballero OL, Orr BA, et al. Yes-associated protein 1 is activated and functions as an oncogene in meningiomas. Mol Cancer Res. 2012;10:904–913.
Lin KC, Park HW, Guan KL. Regulation of the Hippo pathway transcription factor TEAD. Trends Biochem Sci. 2017;42:862–872.
Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163:811–828.
Antonescu CR, Le Loarer F, Mosquera J-M, et al. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes Chromosomes Cancer. 2013;52:775–784.
Sievers P, Chiang J, Schrimpf D, et al. YAP1-fusions in pediatric NF2-wildtype meningioma. Acta Neuropathol. 2020;139:215–218.
Felmeister AS, Masino AJ, Rivera TJ, et al. The biorepository portal toolkit: an honest brokered, modular service oriented software tool set for biospecimen-driven translational research. BMC Genomics. 2016;17(suppl 4):434.
Kelly BJ, Fitch JR, Hu Y, et al. Churchill: an ultra-fast, deterministic, highly scalable and balanced parallelization strategy for the discovery of human genetic variation in clinical and population-scale genomics. Genome Biol. 2015;16:6.
Cibulskis K, Lawrence MS, Carter SL, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31:213–219.
Zhang J, Walsh MF, Wu G, et al. Germline mutations in predisposition genes in pediatric cancer. N Engl J Med. 2015;373:2336–2346.
Koboldt DC, Zhang Q, Larson DE, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012;22:568–576.
Haas BJ, Dobin A, Li B, et al. Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods. Genome Biol. 2019;20:1–16.
Wang K, Singh D, Zeng Z, et al. MapSplice: accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res. 2010;38:e178.
Kim D, Salzberg SL. TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol. 2011;12:R72.
Nicorici D, Satalan M, Edgren H, et al. FusionCatcher—a tool for finding somatic fusion genes in paired-end RNA-sequencing data. Cold Spring Harbor Laboratory; 2014.
Ge H, Liu K, Juan T, et al. FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics. 2011;27:1922–1928.
Davidson NM, Majewski IJ, Oshlack A. JAFFA: high sensitivity transcriptome-focused fusion gene detection. Genome Med. 2015;7:43.
Jia W, Qiu K, He M, et al. SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data. Genome Biol. 2013;14:R12.
Patro R, Duggal G, Love MI, et al. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods. 2017;14:417–419.
Kothari V, Wei I, Shankar S, et al. Outlier kinase expression by RNA sequencing as targets for precision therapy; 2013.
Cerami E, Gao J, Dogrusoz U, et al. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–404.
Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.
Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555:469–474.
Serrano J, Snuderl M. Whole genome DNA methylation analysis of human glioblastoma using Illumina BeadArrays. Methods Mol Biol. 2018;1741:31–51.
Pajtler KW, Witt H, Sill M, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27:728–743.
Iglesias-Bexiga M, Castillo F, Cobos ES, et al. WW domains of the yes-kinase-associated-protein (YAP) transcriptional regulator behave as independent units with different binding preferences for PPxY motif-containing ligands. PLoS One. 2015;10:1–22.
Chen HI, Sudol M. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc Natl Acad Sci USA. 1995;92:7819–7823.
Zhao B, Ye X, Yu J, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008;22:1962–1971.
Ehmer U, Sage J. Control of proliferation and cancer growth by the hippo signaling pathway. Mol Cancer Res. 2016;14:127–140.
Li Y, Wing Fong K, Tang M, et al. Fam118B, a newly identified component of Cajal bodies, is required for Cajal body formation, snRNP biogenesis and cell viability. J Cell Sci. 2014;127:2029–2039.
Andreiuolo F, Varlet P, Tauziède-Espariat A, et al. Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features. Brain Pathol. 2019;29:205–216.
Huntoon K, Pluto CP, Ruess L, et al. Sporadic pediatric meningiomas: a neuroradiological and neuropathological study of 15 cases. J Neurosurg Pediatr. 2017;20:141–148.
Ravindranath K, Vasudevan MC, Pande A, et al. Management of pediatric intracranial meningiomas: an analysis of 31 cases and review of literature. Childs Nerv Syst. 2013;29:573–582.
Livingston JH, Stivaros S, Warren D, et al. Intracranial calcification in childhood: a review of aetiologies and recognizable phenotypes. Dev Med Child Neurol. 2014;56:612–626.
Striedinger K, VandenBerg SR, Baia GS, et al. The neurofibromatosis 2 tumor suppressor gene product, merlin, regulates human meningioma cell growth by signaling through YAP. Neoplasia. 2008;10:1204–1212.
Tanahashi K, Natsume A, Ohka F, et al. Activation of yes-associated protein in low-grade meningiomas is regulated by merlin, cell density, and extracellular matrix stiffness. J Neuropathol Exp Neurol. 2015;74:704–709.
Sebio A, Lenz HJ. Molecular pathways: Hippo signaling, a critical tumor suppressor. Clin Cancer Res. 2015;21:5002–5007.
Pajtler KW, Wei Y, Okonechnikov K, et al. YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. Nat Commun. 2019;10:1–16.
Kosugi S, Hasebe M, Tomita M, et al. Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci USA. 2009;106:10171–10176.
Jiang C, Song T, Li J, et al. RAS promotes proliferation and resistances to apoptosis in meningioma. Mol Neurobiol. 2017;54:779–787.
Carstens C, Messe E, Zang KD, et al. Human KRAS oncogene expression in meningioma. Cancer Lett. 1988;43:37–41.
Sharma S, Ray S, Mukherjee S, et al. Multipronged quantitative proteomic analyses indicate modulation of various signal transduction pathways in human meningiomas. Proteomics. 2015;15:394–407.
Mawrin C, Sasse T, Kirches E, et al. Different activation of mitogen-activated protein kinase and Akt signaling is associated with aggressive phenotype of human meningiomas. Clin Cancer Res. 2005;11:4074–4082.
Johnson MD, Woodard A, Kim P, et al. Evidence for mitogen-associated protein kinase activation and transduction of mitogenic signals by platelet-derived growth factor in human meningioma cells. J Neurosurg. 2001;94:293–300.
Arnli MB, Backer-Grøndahl T, Ytterhus B, et al. Expression and clinical value of EGFR in human meningiomas. PeerJ. 2017;2017:e3140.
Ferluga S, Baiz D, Hilton DA, et al. Constitutive activation of the EGFR–STAT1 axis increases proliferation of meningioma tumor cells. Neurooncology Adv. 2020;2:vdaa008.
Yun S, Koh JM, Lee KS, et al. Expression of c-MET in invasive meningioma. J Pathol Transl Med. 2015;49:44–51.
Norden AD, Raizer JJ, Abrey LE, et al. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol. 2010;96:211–217.
Lai AZ, Abella JV, Park M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol. 2009;19:542–551.