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.
Van Roy
Nadine
N
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Vandesompele
Jo
J
Menten
Björn
B
Nilsson
Helén
H
De Smet
Els
E
Rocchi
Mariano
M
De Paepe
Anne
A
Påhlman
Sven
S
Speleman
Frank
F
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
D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C071660:ZFHX3 protein, human