title: SMARCB1 deletion by a complex three-way chromosomal translocation in an extrarenal malignant rhabdoid tumor.
abstract: Rhabdoid tumors (RTs) are highly aggressive malignant neoplasms of early childhood that arise in the kidney, brain, and extrarenal sites. The disease is genetically defined by biallelic disruption of the SMARCB1/INI1/SNF5 tumor suppressor gene, a core component of the ATP-dependent chromatin remodeling SWI/SNF complex. The molecular changes leading to SMARCB1 alterations in RTs are heterogeneous, including germline or constitutional inactivating mutations, partial or total gene deletions, copy number neutral loss of heterozygosity, and, less commonly, reciprocal translocations. We report a novel three-way chromosomal rearrangement, which was identified by conventional cytogenetic and sequential fluorescence in situ hybridization studies as the underlying molecular mechanism of the loss of SMARCB1 in an extrarenal RT. This case highlights the heterogeneity of genetic events that may lead to the loss of SMARCB1 and the development of RTs.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: armita.bahrami@stjude.org.
authors.forename: Armita
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Seungjae
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, The University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Kari D
authors.initials: KD
authors.lastname: Caradine
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Folpe
mesh_terms: D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D016707:Tissue Fixation; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords: FISH; INI1; Rhabdoid tumor; SMARCB1; conventional cytogenetic; sequential G-banded FISH