title: Whole exome sequencing in a case of sporadic multiple meningioma reveals shared NF2, FAM109B, and TPRXL mutations, together with unique SMARCB1 alterations in a subset of tumor nodules.
abstract: Meningiomas are common intracranial tumors derived from arachnoid cells. Multiple meningiomas are occasionally present even in patients with no history of neurofibromatosis type 2, a condition that can cause the formation of this neoplasm. Previous studies have shown that most multiple meningiomas are monoclonal in origin. In this study, exome sequencing was performed on four meningiomas and the corresponding peripheral blood DNA from a 61-year-old woman with sporadic multiple meningioma. At least three common mutational events (at the NF2, FAM109B, and TPRXL genes) were detected in the tumors' DNA when they were compared with the lymphocyte DNA from the patient as control. Additionally, an array of unique mutations was detected in each tumor, including in SMARCB1 in two of the samples, a gene whose alteration leads to the development of meningioma. Mutations in other genes, such as IRS4, GULP1, NHSL1, and C10orf53, accounted for one alteration in each meningioma nodule. Our data suggest a monoclonal origin of the meningiomas in this patient, although the numerous alterations contained in each sample indicated multiple secondary variable changes in each tumor nodule. Whether the alterations described in this work are drivers of tumorigenesis or are simply passengers requires further study.
authors.affiliation: Research Unit, La Paz University Hospital, IdiPAZ, Madrid, Spain. Electronic address: migtorres.martin@gmail.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres-Martín
authors.affiliation: Neurosurgery and Radiosurgery Department, Ruber International Hospital, Madrid, Spain.
authors.forename: M Elena
authors.initials: ME
authors.lastname: Kusak
authors.affiliation: Neurosurgery Department, La Paz University Hospital, IdiPAZ, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Isla
authors.affiliation: Human Cytogenetics Laboratory, Federal University of Pará, Belém, Brazil.
authors.forename: Rommel R
authors.initials: RR
authors.lastname: Burbano
authors.affiliation: Genetics and Molecular Biology Laboratory, Federal University of Piauí, Parnaíba, Brazil.
authors.forename: Giovanny R
authors.initials: GR
authors.lastname: Pinto
authors.affiliation: Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Melendez
authors.affiliation: Department of Biochemistry and Genetics, University of Navarra School of Sciences, Pamplona, Spain.
authors.forename: Javier S
authors.initials: JS
authors.lastname: Castresana
authors.affiliation: Research Unit, La Paz University Hospital, IdiPAZ, Madrid, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008577:Meningeal Neoplasms / Q000235:genetics; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D025581:Neurofibromin 2 / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C454119:GULP1 protein, human; C107686:IRS4 protein, human; D055504:Insulin Receptor Substrate Proteins; C502541:NHSL1 protein, human; D009363:Neoplasm Proteins; D025581:Neurofibromin 2; C548333:PHETA2 protein, human; D011506:Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; D033921:Vesicular Transport Proteins
keywords: Multiple meningioma; NF2; SMARCB1; neurofibromatosis type 2; whole exome sequence