Integrated cytogenetic and high-resolution array CGH analysis of genomic alterations associated with MYCN amplification

A. Pandita, J. Bayani, J. Paderova, P. Marrano, C. Graham, Michael Barrett, M. Prasad, M. Zielenska, J. A. Squire

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Amplification of oncogenes and closely linked flanking genes is common in some types of cancer and can be associated with complex chromosome rearrangements and/or co-amplification of non-syntenic chromosomal regions. To better understand the etiology and structural complexity of focal MYCN amplicons in human neuronal cancer, we investigated the precise chromosomal locations of high copy number genomic regions in MYCN amplified cell lines. An integrated cytogenetic map of the MYCN amplicon was created using high-resolution array CGH, spectral karyotyping (SKY), multi-color banding (mBAND), and fluorescence in situ hybridization (FISH) in 4 human neuronal tumor cell lines. The evidence of complex intra- and inter-chromosomal events, providing clues concerning the nature of the genomic mechanisms that contributed to the process of MYCN amplification, was observed. The presence of multiple co-amplified syntenic or non-syntenic sequences in the MYCN amplicon is quite intriguing. MYCN is usually centrally located in the amplicon; however, the structure and complexity of the amplicons were highly variable. It is noteworthy that clusters of unstable repetitive regions characterized by CNV sequences were present throughout the regions encompassed by MYCN gene amplification, and these sequences could provide a mechanism to destabilize this region of the genome. Complex structural rearrangements involving genomic losses and gains in the 2p24 region lead to MYCN amplification and that these rearrangements can trigger amplification events.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalCytogenetic and Genome Research
Volume134
Issue number1
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Cytogenetics
Spectral Karyotyping
Gene Amplification
Nucleic Acid Repetitive Sequences
Tumor Cell Line
Fluorescence In Situ Hybridization
Oncogenes
Neoplasms
Color
Chromosomes
Genome
Cell Line
Genes

Keywords

  • aCGH
  • FISH
  • mBAND
  • MYCN
  • Neuroblastoma
  • Retinoblastoma

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Integrated cytogenetic and high-resolution array CGH analysis of genomic alterations associated with MYCN amplification. / Pandita, A.; Bayani, J.; Paderova, J.; Marrano, P.; Graham, C.; Barrett, Michael; Prasad, M.; Zielenska, M.; Squire, J. A.

In: Cytogenetic and Genome Research, Vol. 134, No. 1, 04.2011, p. 27-39.

Research output: Contribution to journalArticle

Pandita, A, Bayani, J, Paderova, J, Marrano, P, Graham, C, Barrett, M, Prasad, M, Zielenska, M & Squire, JA 2011, 'Integrated cytogenetic and high-resolution array CGH analysis of genomic alterations associated with MYCN amplification', Cytogenetic and Genome Research, vol. 134, no. 1, pp. 27-39. https://doi.org/10.1159/000324698
Pandita, A. ; Bayani, J. ; Paderova, J. ; Marrano, P. ; Graham, C. ; Barrett, Michael ; Prasad, M. ; Zielenska, M. ; Squire, J. A. / Integrated cytogenetic and high-resolution array CGH analysis of genomic alterations associated with MYCN amplification. In: Cytogenetic and Genome Research. 2011 ; Vol. 134, No. 1. pp. 27-39.
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