Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer
نویسندگان
چکیده
The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification.
منابع مشابه
Duplication of N-MYC at its resident site 2p24 may be a mechanism of activation alternative to amplification in human neuroblastoma cells.
Amplification of the human N-MYC proto-oncogene is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. N-MYC maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of N-MYC during amplification. Previous studies had suggested that in ce...
متن کاملPaola Dal Cin
Double minutes (dmin) and homogeneously staining regions (hsr) are the cytogenetic hallmarks of genomic amplification in cancer, more common in solid tumors than in hematologic malignancies. Double minute chromosomes are seen primarily in acute myeloid leukemia, with amplification of the MYC oncogene or, less frequently, the MLL transcription factor (Rayeroux and Campbell 2009). Both normal and...
متن کاملMYCN is retained in single copy at chromosome 2 band p23-24 during amplification in human neuroblastoma cells.
Amplification of the human N-myc protooncogene, MYCN, is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. MYCN maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of MYCN during amplification. We have employed fluorescence in situ...
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Two human neuroendocrine tumor cell lines derived from a colon carcinoma contain either numerous double minute chromosomes (COLO 320 DM) or a homogeneously staining marker chromosome (COLO 320 HSR). We found amplification and enhanced expression of the cellular oncogene c-myc in both COLO 320 DM and HSR cells, and we were able to show that the homogeneously staining regions of the COLO 320 HSR ...
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عنوان ژورنال:
دوره 42 شماره
صفحات -
تاریخ انتشار 2014