title: Translocation-excision-deletion-amplification mechanism leading to nonsyntenic coamplification of MYC and ATBF1.
abstract: Despite oncogene amplification being a characteristic of many tumor types, the mechanisms leading to amplicon formation have remained largely unresolved. In this study, we used a combinatorial approach of fluorescence in situ hybridization and single-nucleotide polymorphism chip gene copy number analyses to unravel the mechanism leading to nonsyntenic coamplification of MYC and ATBF1 in SJNB-12 cells. To explain our findings, we propose a complex series of events consisting of multiple double-strand breaks, accompanied (or triggered) by the formation of a reciprocal translocation t(8;16), as well as excisions and deletions near the translocation breakpoints. This study provides evidence for a translocation-excision-deletion-amplification sequence of events rather than a breakage-fusion-bridge model, which has been more frequently proposed to explain proto-oncogene amplification. Furthermore, it illustrates the power of presently available tools for detailed analysis of the complex rearrangements that accompany amplicon formation.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
authors.forename: Helén
authors.initials: H
authors.lastname: Nilsson
authors.forename: Els
authors.initials: E
authors.lastname: De Smet
authors.forename: Mariano
authors.initials: M
authors.lastname: Rocchi
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D045744:Cell Line, Tumor; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D005784:Gene Amplification; D017353:Gene Deletion; D016259:Genes, myc; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C071660:ZFHX3 protein, human