Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors

被引：10

作者：

Engelhardt, Sophie ^{[1
]}

Behling, Felix ^{[2
,3
]}

Beschorner, Rudi ^{[1
,3
]}

Eckert, Franziska ^{[3
,4
,5
]}

Kohlhof, Patricia ^{[6
]}

Tatagiba, Marcos ^{[2
,3
]}

Tabatabai, Ghazaleh ^{[3
,5
,7
,8
]}

Schuhmann, Martin U. ^{[2
,3
,9
]}

Ebinger, Martin ^{[10
]}

Schittenhelm, Jens ^{[1
,3
]}

机构：

[1] Eberhard Karls Univ Tuebingen, Univ Hosp Tuebingen, Inst Pathol & Neuropathol, Dept Neuropathol, Calwerstr 3, D-72076 Tubingen, Germany

[2] Eberhard Karls Univ Tuebingen, Univ Hosp Tuebingen, Dept Neurosurg, D-72076 Tubingen, Germany

[3] Eberhard Karls Univ Tuebingen, Univ Hosp Tuebingen, Comprehens Canc Ctr Tuebingen Stuttgart, Ctr Neurooncol, Tubingen, Germany

[4] Univ Hosp Tuebingen, Dept Radiat Oncol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany

[5] German Consortium Translat Canc Res DKTK, DKFZ Partner Site Tuebingen, Tubingen, Germany

[6] Katharinenhosp Stuttgart, Inst Pathol, Stuttgart, Germany

[7] Eberhard Karls Univ Tubingen, Hertie Inst Clin Brain Res, Univ Hosp Tubingen, Dept Neurol & Interdisciplinary Neurooncol, D-72076 Tubingen, Germany

[8] Eberhard Karls Univ Tuebingen, Ctr Personalized Med, Tubingen, Germany

[9] Eberhard Karls Univ Tuebingen, Univ Hosp Tuebingen, Dept Neurosurg, Div Pediat Neurosurg, Tubingen, Germany

[10] Eberhard Karls Univ Tuebingen, Childrens Univ Hosp, Dept Pediat Hematol Oncol, Tubingen, Germany

来源：

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2022年 / 148卷 / 04期

关键词：

FGFR1; Pyrosequencing; Low-grade glioma; Mixed neuronal glial tumor; Immunohistochemistry; CENTRAL-NERVOUS-SYSTEM; GENETIC ALTERATIONS; BRAF; CLASSIFICATION; MUTATIONS;

D O I：

10.1007/s00432-021-03906-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations. Methods We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases. Results 368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed. Conclusion FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.

引用

页码：857 / 866

页数：10

共 38 条

[1] IDH-mutant gliomas with additional class-defining molecular events [J].

Ahrendsen, Jared T. ;

Torre, Matthew ;

Meredith, David M. ;

Hornick, Jason L. ;

Reardon, David A. ;

Wen, Patrick Y. ;

Yeo, Kee K. ;

Malinowski, Seth ;

Ligon, Keith L. ;

Ramkissoon, Shakti ;

Alexandrescu, Sanda .

MODERN PATHOLOGY, 2021, 34 (07) :1236-1244

[2] Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group [J].

Ater, Joann L. ;

Zhou, Tianni ;

Holmes, Emiko ;

Mazewski, Claire M. ;

Booth, Timothy N. ;

Freyer, David R. ;

Lazarus, Ken H. ;

Packer, Roger J. ;

Prados, Michael ;

Sposto, Richard ;

Vezina, Gilbert ;

Wisoff, Jeffrey H. ;

Pollack, Ian F. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (21) :2641-2647

[3] FGFR- gene family alterations in low-grade neuroepithelial tumors [J].

Bale, Tejus A. .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2020, 8 (01)

[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] Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma [J].

Ceccarelli, Michele ;

Barthel, Floris P. ;

Malta, Tathiane M. ;

Sabedot, Thais S. ;

Salama, Sofie R. ;

Murray, Bradley A. ;

Morozova, Olena ;

Newton, Yulia ;

Radenbaugh, Amie ;

Pagnotta, Stefano M. ;

Anjum, Samreen ;

Wang, Jiguang ;

Manyam, Ganiraju ;

Zoppoli, Pietro ;

Ling, Shiyun ;

Rao, Arjun A. ;

Grifford, Mia ;

Cherniack, Andrew D. ;

Zhang, Hailei ;

Poisson, Laila ;

Carlotti, Carlos Gilberto, Jr. ;

Tirapelli, Daniela Pretti da Cunha ;

Rao, Arvind ;

Mikkelsen, Tom ;

Lau, Ching C. ;

Yung, W. K. Alfred ;

Rabadan, Raul ;

Huse, Jason ;

Brat, Daniel J. ;

Lehman, Norman L. ;

Barnholtz-Sloan, Jill S. ;

Zheng, Siyuan ;

Hess, Kenneth ;

Rao, Ganesh ;

Meyerson, Matthew ;

Beroukhim, Rameen ;

Cooper, Lee ;

Akbani, Rehan ;

Wrensch, Margaret ;

Haussler, David ;

Aldape, Kenneth D. ;

Laird, Peter W. ;

Gutmann, David H. ;

Noushmehr, Houtan ;

Iavarone, Antonio ;

Verhaak, Roel G. W. .

CELL, 2016, 164 (03) :550-563

[6] Pilocytic astrocytoma: pathology, molecular mechanisms and markers [J].

Collins, V. Peter ;

Jones, David T. W. ;

Giannini, Caterina .

ACTA NEUROPATHOLOGICA, 2015, 129 (06) :775-788

[7] Management of pediatric low-grade glioma [J].

de Blank, Peter ;

Bandopadhayay, Pratiti ;

Haas-Kogan, Daphne ;

Fouladi, Maryam ;

Fangusaro, Jason .

CURRENT OPINION IN PEDIATRICS, 2019, 31 (01) :21-27

[8] ATRX immunostaining predicts IDH and H3F3A status in gliomas [J].

Ebrahimi, Azadeh ;

Skardelly, Marco ;

Bonzheim, Irina ;

Ott, Ines ;

Muehleisen, Helmut ;

Eckert, Franziska ;

Tabatabai, Ghazaleh ;

Schittenhelm, Jens .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2016, 4 :60

[9] cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAFV600E mutation [J].

Ellison, David W. ;

Hawkins, Cynthia ;

Jones, David T. W. ;

Onar-Thomas, Arzu ;

Pfister, Stefan M. ;

Reifenberger, Guido ;

Louis, David N. .

ACTA NEUROPATHOLOGICA, 2019, 137 (04) :683-687

[10] Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1) [J].

Fisher, Michael J. ;

Jones, David T. W. ;

Li, Yimei M. ;

Guo, Xiaofan ;

Sonawane, Poonam S. ;

Waanders, Angela J. ;

Phillips, Joanna J. ;

Weiss, William A. ;

Resnick, Adam C. ;

Gosline, Sara ;

Banerjee, Jineta ;

Guinney, Justin ;

Gnekow, Astrid ;

Kandels, Daniela ;

Foreman, Nicholas K. ;

Korshunov, Andrey ;

Ryzhova, Marina ;

Massimi, Luca ;

Gururangan, Sri ;

Kieran, Mark W. ;

Wang, Zhihong ;

Fouladi, Maryam ;

Sato, Mariko ;

Ora, Ingrid ;

Holm, Stefan ;

Markham, Stephen J. ;

Beck, Pengbo ;

Jaeger, Natalie ;

Wittmann, Andrea ;

Sommerkamp, Alexander C. ;

Sahm, Felix ;

Pfister, Stefan M. ;

Gutmann, David H. .

ACTA NEUROPATHOLOGICA, 2021, 141 (04) :605-617

← 1 2 3 4 →