Translocation–excision–deletion–amplification mechanism leading to nonsyntenic coamplification of MYC and ATBF1

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. © 2005 Wiley‐Liss, Inc.

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