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. 2008:(39):25-31.
doi: 10.1093/jncimonographs/lgn011.

Characterization of MYC translocations in multiple myeloma cell lines

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Characterization of MYC translocations in multiple myeloma cell lines

Amel Dib et al. J Natl Cancer Inst Monogr. 2008.

Abstract

Translocations involving an MYC gene (c >> N >>L) are very late tumor progression events and provide a paradigm for secondary translocations in multiple myeloma. Using a combination of fluorescent in situ hybridization and comparative genomic hybridization arrays (aCGH), we have identified rearrangements of an MYC gene in 40 of 43 independent myeloma cell lines. A majority of MYC translocations involve an Ig locus (IgH > Iglambda >> Igkappa), but the breakpoints only infrequently occur near or within switch regions or V(D)J sequences. Surprisingly, about 40% of MYC translocations do not involve an Ig locus. The MYC translocations mostly are nonreciprocal translocations or insertions, often with the involvement of three chromosomes and sometimes with associated duplication, amplification, inversion, and other associated chromosomal abnormalities. High-density aCGH analyses should facilitate the cloning of MYC breakpoints, enabling the determination of their structures and perhaps elucidating how rearrangements not involving an Ig gene cause dysregulation of an MYC gene.

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Figures

Figure 1
Figure 1
Examples of molecular cytogenetic analyses of MYC rearrangements in multiple myeloma. A, B) Primary data and C) schematic representations of FISH analyses of metaphase chromosomes found in different cell lines. MYC probe is red and Ig C (3′ enhancer) probe is green. A) Normal chromosome 8 (CHR 8) and amplification of MYC gene and flanking sequences on der(8) in KAS-6 HMCL; B) normal chromosome 2 (CHR 2) and juxtaposition of Ck probe from 2p12 near N-MYC at 2p25 on inv(2)(p25p12) in PE-2 HMCL. The Cκ probe cross-hybridizes with unknown sequences at 2q11 on both CHR 2 and on inv(2)(p25p12). C) Diagrams of some of the structural rearrangements involving c-MYC that have been identified by FISH analyses in different HMCL and primary MM tumor samples.

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