title: Localization of centromeric breaks in head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) have very complex karyotypes that show all types of structural rearrangements. The most frequent aberrations are whole-arm translocations, which appear to have their breakpoints in centromeric or pericentromeric regions. We aimed to pinpoint the exact location of the breakpoints of these marker chromosomes with high-resolution cytogenetic and genetic analyses using microarray comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA), and fiber fluorescence in situ hybridization (FISH). Among the seven cell lines in this study, six (84%) harbored one or more centromeric breakpoints or whole-arm translocations. In total, microarray CGH identified 163 breakpoints, 47 (29%) of which were in centromeric regions. Microarray CGH and MLPA results indicated that the translocation breakpoints were localized between the microarray oligonucleotide clones and MLPA probes closest to the centromere. High-resolution fiber-FISH revealed adjacent or minimally overlapping signals of probes that recognize the pericentromeric sequences of the two participating chromosomes. This indicates that whole chromosome arm translocation breakpoints occur within the pericentromeric chromatin and not the centromere core sequences.
authors.affiliation: Department of Otolaryngology, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Jorge García
authors.initials: JG
authors.lastname: Martínez
authors.forename: Jhudit
authors.initials: J
authors.lastname: Pérez-Escuredo
authors.forename: José Luis
authors.initials: JL
authors.lastname: Llorente
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.forename: Mario A
authors.initials: MA
authors.lastname: Hermsen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002503:Centromere / Q000235:genetics*; D019457:Chromosome Breakage; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018404:Isochromosomes / Q000235:genetics; D008954:Models, Biological; D060885:Multiplex Polymerase Chain Reaction; D020411:Oligonucleotide Array Sequence Analysis; D014178:Translocation, Genetic