title: Mutational Analysis of Recurrent Meningioma Progressing From Atypical to Rhabdoid Subtype.
abstract: BACKGROUND
  Rhabdoid meningioma is rare aggressive meningioma histological subtype that develops predominantly through progression from less malignant tumors. Owing to its low incidence, this tumor's biological background is unknown. The aim of this study was to profile somatic mutations in 4 meningioma samples from the same patient, derived previously from 4 subsequent tumor resections.
  
  
  METHODS
  A 58-year-old woman presented with recurrent meningioma progressing from atypical to rhabdoid subtype. Four tumor samples that represent a primary tumor (atypical GII) and 3 recurrent tumors that were subsequently removed (anaplastic GIII, rhabdoid GIII, and anaplastic/rhabdoid GIII) from this patient were subjected to mutational analysis of coding sequences of 952 tumor-related genes. Three mutations were identified in all tumor samples exhibiting a high allelic frequency: ARID1A frameshift deletion, NF2 in-frame deletion, and missense variant of SRSF2. The predicted inactivating effect of ARID1A deletion was confirmed by immunohistochemical staining of tumor sections in which a high proportion of cells lacked protein expression. Additional low-allelic-fraction mutations were observed in all tumor samples, likely representing "passenger," low-effect mutations that reflect a clonal selection of tumor cells through malignant progression of the meningioma.
  
  
  CONCLUSIONS
  The mutation of ARID1A that encodes the subunit of the SWI/SNF complex represents the most likely driver of the tumor's malignant potential. It also may be involved in the acquisition of the rhabdoid phenotype, given that mutations in chromatin remodeling proteins are the hallmark of atypical teratoid/rhabdoid tumors.
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. Electronic address: mbujko@coi.waw.pl.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Bujko
authors.affiliation: Department of Immunology, Medical University of Warsaw, Warsaw, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marcin M
authors.initials: MM
authors.lastname: Machnicki
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Grecka
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Nataliia
authors.initials: N
authors.lastname: Rusetska
authors.affiliation: Department of Experimental and Clinical Neuropathology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Matyja
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kober
authors.affiliation: Department of Neurosurgery, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mandat
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Head and Neck Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Romuald
authors.initials: R
authors.lastname: Krajewski
authors.affiliation: Department of Neurosurgery, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Bonicki
authors.affiliation: Department of Immunology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Stokłosa
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Siedlecki
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018335:Rhabdoid Tumor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: Anaplastic; Atypical; Meningioma; Progression; Rhabdoid; Somatic mutation