title: Broadening the spectrum of SMARCB1-associated malignant tumors: a case of uterine leiomyosarcoma in a patient with schwannomatosis.
abstract: Schwannomatosis is a tumor predisposition syndrome characterized by development of multiple intracranial, spinal, and peripheral schwannomas. Constitutional alterations in either SMARCB1 or LZTR1 on 22q are responsible of the phenotype. We describe a 34-year-old woman who developed multiple benign peripheral sheath tumors and a uterine leiomyosarcoma. The patient carried a de novo constitutional alteration in exon 8 of SMARCB1, c.1118G > A, which destroyed the splice donor site of intron 8. Two schwannomas and the leiomyosarcoma of the patient retained the SMARCB1 mutation; in addition, the tumors showed loss of the normal chromosome 22. In conclusion, our findings enlarged the spectrum of SMARCB1-predisposing tumors and demonstrated, for the first time, the association of a malignant smooth muscle tumor to schwannomatosis. Therefore, clinicians should definitely be aware that a constitutional SMARCB1 mutation, which mainly predisposes to benign nerve sheath tumors, may also predispose to aggressive neoplasms throughout life, within an unexpected spectrum.
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, 50139, Florence, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paganini
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, 50139, Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sestini
authors.affiliation: Department of Pathology and Molecular Genetics, Treviso General Hospital, 31100,Treviso, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Cacciatore
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, 50139, Florence, Italy.
authors.forename: Gabriele L
authors.initials: GL
authors.lastname: Capone
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, 50139, Florence, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Candita
authors.affiliation: Department of Oncology, Treviso General Hospital, 31100, Treviso, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Paolello
authors.affiliation: Department of Pathology and Molecular Genetics, Treviso General Hospital, 31100,Treviso, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Sbaraglia
authors.affiliation: Department of Pathology and Molecular Genetics, Treviso General Hospital, 31100,Treviso, Italy. Electronic address: apdeitos@ulss.tv.it.
authors.forename: Angelo P
authors.initials: AP
authors.lastname: Dei Tos
authors.affiliation: Department of Pathology and Molecular Genetics, Treviso General Hospital, 31100,Treviso, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, 50139, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Papi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000235:genetics*; D060885:Multiplex Polymerase Chain Reaction; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics*; D017253:Neurofibromatoses / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000071796:SMARCB1 Protein; D012878:Skin Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords: LZTR1; Leiomyosarcoma; NF2; SMARCB1; Schwannomatosis