Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)

被引：44

作者：

Fisher, Michael J. ^{[1
]}

Jones, David T. W. ^{[2
,3
]}

Li, Yimei M. ^{[4
]}

Guo, Xiaofan ^{[5
]}

Sonawane, Poonam S. ^{[6
]}

Waanders, Angela J. ^{[1
,23
]}

Phillips, Joanna J. ^{[7
]}

Weiss, William A. ^{[8
]}

Resnick, Adam C. ^{[6
]}

Gosline, Sara ^{[9
,24
]}

Banerjee, Jineta ^{[9
]}

Guinney, Justin ^{[9
]}

Gnekow, Astrid ^{[10
]}

Kandels, Daniela ^{[10
]}

Foreman, Nicholas K. ^{[11
]}

Korshunov, Andrey ^{[12
]}

Ryzhova, Marina ^{[13
]}

Massimi, Luca ^{[14
,28
]}

Gururangan, Sri ^{[15
]}

Kieran, Mark W. ^{[16
,25
]}

Wang, Zhihong ^{[17
,26
]}

Fouladi, Maryam ^{[18
,27
]}

Sato, Mariko ^{[19
]}

Ora, Ingrid ^{[20
]}

Holm, Stefan ^{[21
]}

Markham, Stephen J. ^{[1
]}

Beck, Pengbo ^{[2
,3
]}

Jaeger, Natalie ^{[2
,3
]}

Wittmann, Andrea ^{[2
]}

Sommerkamp, Alexander C. ^{[2
,3
]}

Sahm, Felix ^{[12
]}

Pfister, Stefan M. ^{[2
,3
,22
]}

Gutmann, David H. ^{[5
]}

机构：

[1] Childrens Hosp Philadelphia, Div Oncol, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA

[2] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[3] German Canc Res Ctr, Pediat Glioma Res Grp, Heidelberg, Germany

[4] Univ Penn, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA

[5] Washington Univ, Dept Neurol, Sch Med, 660 South Euclid Ave,Box 8111, St Louis, MO 63110 USA

[6] Childrens Hosp Philadelphia, Div Neurosurg, Philadelphia, PA 19104 USA

[7] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[8] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[9] Sage Bionetworks, Seattle, WA USA

[10] Univ Augsburg, Fac Med, Augsburg, Germany

[11] Univ Colorado, Denver, CO 80202 USA

[12] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany

[13] NN Burdenko Neurosurg Res Ctr, Dept Neuropathol, Moscow, Russia

[14] IRCCS, Fdn Policlin A Gemelli, Rome, Italy

[15] UF Hlth Shands Hosp, Dept Neurosurg, Gainesville, FL USA

[16] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA

[17] Childrens Hosp Michigan, Div Hematol Oncol, Detroit, MI 48201 USA

[18] Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA

[19] Univ Iowa, Stead Family Childrens Hosp, Div Hematol Oncol, Iowa City, IA USA

[20] Lund Univ, Canc Ctr, Lund, Sweden

[21] Karolinska Univ Hosp, Stockholm, Sweden

[22] Heidelberg Univ Hosp, Dept Pediat Oncol Hematol Immunol & Pulmonol, Heidelberg, Germany

[23] Lurie Childrens Hosp Chicago, Div Hematol Oncol, Chicago, IL USA

[24] Pacific Northwest Natl Lab, Seattle, WA USA

[25] Bristol Myers Squibb, Lawrenceville, NJ USA

[26] Childrens Hosp Richmond, Div Hematol & Oncol, Richmond, VA USA

[27] Nationwide Childrens Hosp, Div Hematol & Oncol, Columbus, OH USA

[28] A Gemelli Hosp, Pediat Neurosurg, Rome, Italy

来源：

ACTA NEUROPATHOLOGICA | 2021年 / 141卷 / 04期

关键词：

Pilocytic astrocytoma; Pediatric brain tumor; Neurofibromatosis; Methylation; FGFR1;

D O I：

10.1007/s00401-021-02276-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.

引用

页码：605 / 617

页数：13

共 32 条

[1] Children with 5′-end &ITNF1&IT gene mutations are more likely to have glioma [J].

Anastasaki, Corina ;

Morris, Stephanie M. ;

Gao, Feng ;

Gutmann, David H. .

NEUROLOGY-GENETICS, 2017, 3 (05)

[2] Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2 [J].

Abaza, MM ;

Makariou, E ;

Armstrong, M ;

Lalwani, AK .

LARYNGOSCOPE, 1996, 106 (06) :694-699

[3] MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism [J].

Bandopadhayay, Pratiti ;

Ramkissoon, Lori A. ;

Jain, Payal ;

Bergthold, Guillaume ;

Wala, Jeremiah ;

Zeid, Rhamy ;

Schumacher, Steven E. ;

Urbanski, Laura ;

O'Rourke, Ryan ;

Gibson, William J. ;

Pelton, Kristine ;

Ramkissoon, Shakti H. ;

Han, Harry J. ;

Zhu, Yuankun ;

Choudhari, Namrata ;

Silva, Amanda ;

Boucher, Katie ;

Henn, Rosemary E. ;

Kang, Yun Jee ;

Knoff, David ;

Paolella, Brenton R. ;

Gladden-Young, Adrianne ;

Varlet, Pascale ;

Pages, Melanie ;

Horowitz, Peleg M. ;

Federation, Alexander ;

Malkin, Hayley ;

Tracy, Adam A. ;

Seepo, Sara ;

Ducar, Matthew ;

Van Hummelen, Paul ;

Santi, Mariarita ;

Buccoliero, Anna Maria ;

Scagnet, Mirko ;

Bowers, Daniel C. ;

Giannini, Caterina ;

Puget, Stephanie ;

Hawkins, Cynthia ;

Tabori, Uri ;

Klekner, Almos ;

Bognar, Laszlo ;

Burger, Peter C. ;

Eberhart, Charles ;

Rodriguez, Fausto J. ;

Hill, D. Ashley ;

Mueller, Sabine ;

Haas-Kogan, Daphne A. ;

Phillips, Joanna J. ;

Santagata, Sandro ;

Stiles, Charles D. .

NATURE GENETICS, 2016, 48 (03) :273-282

[4] DNA methylation-based classification of central nervous system tumours [J].

Capper, David ;

Jones, David T. W. ;

Sill, Martin ;

Hovestadt, Volker ;

Schrimpf, Daniel ;

Sturm, Dominik ;

Koelsche, Christian ;

Sahm, Felix ;

Chavez, Lukas ;

Reuss, David E. ;

Kratz, Annekathrin ;

Wefers, Annika K. ;

Huang, Kristin ;

Pajtler, Kristian W. ;

Schweizer, Leonille ;

Stichel, Damian ;

Olar, Adriana ;

Engel, Nils W. ;

Lindenberg, Kerstin ;

Harter, Patrick N. ;

Braczynski, Anne K. ;

Plate, Karl H. ;

Dohmen, Hildegard ;

Garvalov, Boyan K. ;

Coras, Roland ;

Hoelsken, Annett ;

Hewer, Ekkehard ;

Bewerunge-Hudler, Melanie ;

Schick, Matthias ;

Fischer, Roger ;

Beschorner, Rudi ;

Schittenhelm, Jens ;

Staszewski, Ori ;

Wani, Khalida ;

Varlet, Pascale ;

Pages, Melanie ;

Temming, Petra ;

Lohmann, Dietmar ;

Selt, Florian ;

Witt, Hendrik ;

Milde, Till ;

Witt, Olaf ;

Aronica, Eleonora ;

Giangaspero, Felice ;

Rushing, Elisabeth ;

Scheurlen, Wolfram ;

Geisenberger, Christoph ;

Rodriguez, Fausto J. ;

Becker, Albert ;

Preusser, Matthias .

NATURE, 2018, 555 (7697) :469-+

[5] Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional Properties [J].

Chen, Yi-Hsien ;

McGowan, Lucy D'Agostino ;

Cimino, Patrick J. ;

Dahiya, Sonika ;

Leonard, Jeffrey R. ;

Lee, Da Yong ;

Gutmann, David H. .

CELL REPORTS, 2015, 10 (11) :1899-1912

[6] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[7] Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age [J].

Fontebasso, Adam M. ;

Shirinian, Margret ;

Khuong-Quang, Dong-Anh ;

Bechet, Denise ;

Gayden, Tenzin ;

Kool, Marcel ;

De Jay, Nicolas ;

Jacob, Karine ;

Gerges, Noha ;

Hutter, Barbara ;

Seker-Cin, Huriye ;

Witt, Hendrik ;

Montpetit, Alexandre ;

Brunet, Sebastien ;

Lepage, Pierre ;

Bourret, Genevieve ;

Klekner, Almos ;

Bognar, Laszlo ;

Hauser, Peter ;

Garami, Miklos ;

Farmer, Jean-Pierre ;

Montes, Jose-Luis ;

Atkinson, Jeffrey ;

Lambert, Sally ;

Kwan, Tony ;

Korshunov, Andrey ;

Tabori, Uri ;

Collins, V. Peter ;

Albrecht, Steffen ;

Faury, Damien ;

Pfister, Stefan M. ;

Paulus, Werner ;

Hasselblatt, Martin ;

Jones, David T. W. ;

Jabado, Nada .

ONCOTARGET, 2015, 6 (31) :31844-31856

[8] Increased prevalence of brain tumors classified as T2 hyperintensities in neurofibromatosis 1 [J].

Griffith, Jennifer L. ;

Morris, Stephanie M. ;

Mahdi, Jasia ;

Goyal, Manu S. ;

Hershey, Tamara ;

Gutmann, David H. .

NEUROLOGY-CLINICAL PRACTICE, 2018, 8 (04) :283-291

[9] The landscape of genomic alterations across childhood cancers [J].

Groebner, Susanne N. ;

Worst, Barbara C. ;

Weischenfeldt, Joachim ;

Buchhalter, Ivo ;

Kleinheinz, Kortine ;

Rudneva, Vasilisa A. ;

Johann, Pascal D. ;

Balasubramanian, Gnana Prakash ;

Segura-Wang, Maia ;

Brabetz, Sebastian ;

Bender, Sebastian ;

Hutter, Barbara ;

Sturm, Dominik ;

Pfaff, Elke ;

Huebschmann, Daniel ;

Zipprich, Gideon ;

Heinold, Michael ;

Eils, Jurgen ;

Lawerenz, Christian ;

Erkek, Serap ;

Lambo, Sander ;

Waszak, Sebastian ;

Blattmann, Claudia ;

Borkhardt, Arndt ;

Kuhlen, Michaela ;

Eggert, Angelika ;

Fulda, Simone ;

Gessler, Manfred ;

Wegert, Jenny ;

Kappler, Roland ;

Baumhoer, Daniel ;

Burdach, Stefan ;

Kirschner-Schwabe, Renate ;

Kontny, Udo ;

Kulozik, Andreas E. ;

Lohmann, Dietmar ;

Hettmer, Simone ;

Eckert, Cornelia ;

Bielack, Stefan ;

Nathrath, Michaela ;

Niemeyer, Charlotte ;

Richter, Gunther H. ;

Schulte, Johannes ;

Siebert, Reiner ;

Westermann, Frank ;

Molenaar, Jan J. ;

Vassal, Gilles ;

Witt, Hendrik ;

Burkhardt, Birgit ;

Kratz, Christian P. .

NATURE, 2018, 555 (7696) :321-+

[10] Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1) [J].

Guillamo, JS ;

Créange, A ;

Kalifa, C ;

Grill, J ;

Rodriguez, D ;

Doz, F ;

Barbarot, S ;

Zerah, M ;

Sanson, M ;

Bastuji-Garin, S ;

Wolkenstein, P .

BRAIN, 2003, 126 :152-160

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