title: A translocation t(6;14) in two cases of leiomyosarcoma: Molecular cytogenetic and array-based comparative genomic hybridization characterization.
abstract: Leiomyosarcomas are malignant mesenchymal tumors that recapitulate smooth muscle cell differentiation. Tumors are characterized by a genetic heterogeneity with complex karyotypes without a tumor-specific genetic aberration. Their pathobiology is still poorly understood and no specific targeted treatment is currently available for these aggressive tumors. For six leiomyosarcomas, cells were cultured and analyzed by combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) karyotyping. A t(6;14) was identified in two cases. FISH breakpoint mapping of case L1339 reveals a breakpoint at chromosome 6p21.31 close to HMGA1, and a small deletion was observed on the distal side of the gene. A small homozygous deletion was also found in the breakpoint region of chromosome 14q24.1 involving ACTN1. The second case revealed a der(6)t(6;14)(p21.1;q21.3), with a duplication adjacent to the breakpoint at chromosome 6. Confirmatory FISH revealed a second leiomyosarcoma with an aberration at 14q24.1. Alterations at this locus were found in 5% (2 of 39) of the leiomyosarcomas in this study. The other identified breakpoints appeared to be non-recurrent, because they were not detected in other leiomyosarcomas, uterine leiomyomas, undifferentiated spindle cell sarcomas, or undifferentiated pleomorphic sarcomas.
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Marieke A
authors.initials: MA
authors.lastname: de Graaff
authors.affiliation: Department of Molecular Cell Biology, LUMC, Leiden, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: de Jong
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Inge H
authors.initials: IH
authors.lastname: Briaire-de Bruijn
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
authors.affiliation: Department of Molecular Cell Biology, LUMC, Leiden, The Netherlands. Electronic address: k.szuhai@lumc.nl.
authors.forename: Károly
authors.initials: K
authors.lastname: Szuhai
mesh_terms: D000185:Actinin / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods; D025741:HMGA1a Protein / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D046888:Tissue Array Analysis; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C526905:ACTN1 protein, human; D000185:Actinin; D025741:HMGA1a Protein
keywords: FISH; HMGA1; Leiomyosarcoma; array-CGH; soft tissue sarcoma; translocation