Top

Published in:

01-04-2019 | Correspondence

Prognostic significance of NAB2–STAT6 fusion variants and TERT promotor mutations in solitary fibrous tumors/hemangiopericytomas of the CNS: not (yet) clear

Authors: Rob Vogels, Nicolas Macagno, Klaus Griewank, Patricia Groenen, Marian Verdijk, Judy Fonville, Benno Kusters, Dominique Figarella-Branger, Pieter Wesseling, Corinne Bouvier, Uta Flucke, French CNS SFT/HPC Consortium, Dutch CNS SFT/HPC Consortium

Published in: Acta Neuropathologica | Issue 4/2019

Excerpt

Grading of meningeal solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs) of the central nervous system (CNS) is nowadays based on histologic criteria as described in the revised fourth edition of the WHO Classification of CNS tumors [10] or the more recently published, updated version of the Marseille Grading System (MGS) [11]. Histology-based grading of CNS SFTs/HPCs allows for discriminating subgroups with significant differences in prognosis. However, the often piece meal resection of these tumors may hamper adequate evaluation of mitotic activity and necrosis, and thereby assessment of malignancy grade. NAB2–STAT6 fusion is the molecular hallmark of both soft tissue SFTs and CNS SFTs/HPCs, and the resulting fusion protein accumulates in the nucleus and acts as a transcriptional activator of early growth response mediated pathways with STAT6 immunohistochemistry being a very sensitive and specific tool for their diagnosis [5, 8, 12, 14]. For soft tissue SFTs, particular NAB2–STAT6 fusion variants as well as telomerase reverse transcriptase (TERT) promoter mutations leading to telomerase activity and tumor cell immortalization have been reported to have prognostic value. Some studies have included CNS SFTs/HPCs in their cohort, but because of small numbers and lack of (long term) follow-up data the prognostic value of these markers for CNS SFTs/HPCs is still unclear [1‐4, 6, 7, 9, 13, 15, 16]. …

Available only for authorised users

Akaike K, Kurisaki-Arakawa A, Hara K, Suehara Y, Takagi T, Mitani K et al (2015) Distinct clinicopathological features of NAB2–STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential. Hum Pathol 46:347–356. https://doi.org/10.1016/j.humpath.2014.11.018 CrossRefPubMed

Bahrami A, Lee S, Schaefer IM, Boland JM, Patton KT, Pounds S et al (2016) TERT promoter mutations and prognosis in solitary fibrous tumor. Mod Pathol 29:1511–1522. https://doi.org/10.1038/modpathol.2016.126 CrossRefPubMedPubMedCentral

Barthelmeβ S, Geddert H, Boltze C, Moskalev EA, Bieg M, Sirbu H et al (2014) Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2–STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features. Am J Pathol 184:1209–1218. https://doi.org/10.1016/j.ajpath.2013.12.016 CrossRefPubMed

Bertero L, Anfossi V, Osella-Abate S, Disanto MG, Mantovani C, Zenga F et al (2018) Pathological prognostic markers in central nervous system solitary fibrous tumour/hemangiopericytoma: evidence from a small series. PLoS One 13:e0203570. https://doi.org/10.1371/journal.pone.0203570 CrossRefPubMedPubMedCentral

Chmielecki J, Crago AM, Rosenberg M, O’Connor R, Walker SR, Ambrogio L et al (2013) Whole-exome sequencing identifies a recurrent NAB2–STAT6 fusion in solitary fibrous tumors. Nat Genet 45:131–132. https://doi.org/10.1038/ng.2522 CrossRefPubMedPubMedCentral

Chuang IC, Liao KC, Huang HY, Kao YC, Li CF, Huang SC et al (2016) NAB2–STAT6 gene fusion and STAT6 immunoexpression in extrathoracic solitary fibrous tumors: the association between fusion variants and locations. Pathol Int 66:288–296. https://doi.org/10.1111/pin.12408 CrossRefPubMed

Demicco EG, Wani K, Ingram D, Wagner M, Maki RG, Rizzo A et al (2018) TERT promoter mutations in solitary fibrous tumour. Histopathology 73:843–851. https://doi.org/10.1111/his.13703 CrossRefPubMed

Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL (2013) Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol. https://doi.org/10.1038/modpathol.2013.164 CrossRefPubMed

Fritchie KJ, Jin L, Rubin BP, Burger PC, Jenkins SM, Barthelmess S et al (2016) NAB2–STAT6 gene fusion in meningeal hemangiopericytoma and solitary fibrous tumor. J Neuropathol Exp Neurol 75:263–271. https://doi.org/10.1093/jnen/nlv026 CrossRefPubMed

10.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D et al (2016) WHO classification of tumours of the central nervous system, 4th edn. International Agency for Research on Cancer (IARC), Lyon

11.

Macagno N, Vogels R, Appay R, Colin C, Mokhtari K, French CNSSFTHPCC et al (2018) Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients. Brain Pathol. https://doi.org/10.1111/bpa.12613 CrossRefPubMedPubMedCentral

12.

Mohajeri A, Tayebwa J, Collin A, Nilsson J, Magnusson L, von Steyern FV et al (2013) Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Genes Chromosom Cancer 52:873–886. https://doi.org/10.1002/gcc.22083 CrossRefPubMed

13.

Nakada S, Minato H, Nojima T (2016) Clinicopathological differences between variants of the NAB2–STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system. Brain Tumor Pathol 33:169–174. https://doi.org/10.1007/s10014-016-0264-6 CrossRefPubMed

14.

Robinson DR, Wu YM, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS et al (2013) Identification of recurrent NAB2–STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet 45:180–185. https://doi.org/10.1038/ng.2509 CrossRefPubMedPubMedCentral

15.

Tai HC, Chuang IC, Chen TC, Li CF, Huang SC, Kao YC et al (2015) NAB2–STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. Mod Pathol 25:25. https://doi.org/10.1038/modpathol.2015.90 CrossRef

16.

Yuzawa S, Nishihara H, Wang L, Tsuda M, Kimura T, Tanino M et al (2016) Analysis of NAB2–STAT6 gene fusion in 17 cases of meningeal solitary fibrous tumor/hemangiopericytoma: review of the literature. Am J Surg Pathol 40:1031–1040. https://doi.org/10.1097/PAS.0000000000000625 CrossRefPubMed

Title: Prognostic significance of NAB2–STAT6 fusion variants and TERT promotor mutations in solitary fibrous tumors/hemangiopericytomas of the CNS: not (yet) clear
Authors: Rob Vogels
Nicolas Macagno
Klaus Griewank
Patricia Groenen
Marian Verdijk
Judy Fonville
Benno Kusters
Dominique Figarella-Branger
Pieter Wesseling
Corinne Bouvier
Uta Flucke
French CNS SFT/HPC Consortium
Dutch CNS SFT/HPC Consortium
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 4/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-01968-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Prognostic significance of NAB2–STAT6 fusion variants and TERT promotor mutations in solitary fibrous tumors/hemangiopericytomas of the CNS: not (yet) clear

Excerpt

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Excerpt

Please log in to get access to this content

Other articles of this Issue 4/2019

Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease

cIMPACT-NOW update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAFV600E mutation

Tau drives translational selectivity by interacting with ribosomal proteins

Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

Mission not yet completed: on the ups and downs of being the editor of ANP

H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo