title: SMARCB1 involvement in the development of leiomyoma in a patient with schwannomatosis.
abstract: Germline SMARCB1 mutations predispose in schwannomatosis patients to the development of multiple benign schwannomas and, in some cases, meningiomas. Here, we report on a 34-year-old female patient who developed multiple schwannomas at various locations and in addition a leiomyoma of the cervix uteri. She carried a c.362+1G>A mutation that inactivates the donor splice site of exon 3. This mutation caused the schwannomatosis phenotype in this patient and was also demonstrated to be present in her affected mother. The leiomyoma displayed the genetic features that are characteristic for germline SMARCB1 mutation-associated tumors. The mutant allele retained in the tumor, whereas the wild-type allele was lost by loss of heterozygosity. Furthermore, the loss of heterozygosity involved net loss of chromosome 22. An NF2 mutation was not found. However, quantitative polymerase chain reaction suggested that both NF2 copies were lost in the tumor. Immunostaining with a SMARCB1 antibody revealed the mosaic expression pattern that is typical for schwannomatosis-associated tumors. To our knowledge, this is the first reported case of leiomyoma associated with a germline SMARCB1 mutation. As such, it widens the spectrum of benign tumors associated with a germline SMARCB1 mutation.
authors: *Department of Genome Analysis, Academic Medical Center ∥Department of Pathology, VU University Medical Center, Amsterdam §Department of Pathology, Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands †Institute for Human Genetics, University Hospital Muenster, Muenster ‡Institute for Neuropathology, Evangelisches Krankenhaus, Bielefeld, Germany.
authors: Theo J M
authors: TJ
authors: Hulsebos
authors: Susan
authors: S
authors: Kenter
authors: Ulrike
authors: U
authors: Siebers-Renelt
authors: Volkmar
authors: V
authors: Hans
authors: Pieter
authors: P
authors: Wesseling
authors: Uta
authors: U
authors: Flucke
mesh_terms: D000328:Adult; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D016515:Genes, Neurofibromatosis 2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D040941:Heredity; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000737:chemistry / Q000235:genetics*; D019656:Loss of Heterozygosity; D009442:Neurilemmoma / Q000737:chemistry / Q000235:genetics*; D017253:Neurofibromatoses / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D000071796:SMARCB1 Protein; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors