Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma

A report from the children's oncology group

Frederic G. Barr, Fenghai Duan, Lynette M Smith, Donna Gustafson, Mandy Pitts, Sue Hammond, Julie M. Gastier-Foster

Research output: Contribution to journalArticle

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Abstract

Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer that is related to the skeletal muscle lineage and characterized by recurrent chromosomal translocations. Within the ARMS category, there is clinical and genetic heterogeneity, consistent with the premise that "primary" genetic events collaborate with "secondary" events to give rise to subsets with varying clinical features. Previous studies demonstrated that genomic amplification occurs frequently in ARMS. In the current study, we used oligonucleotide arrays to localize two common amplicons to the 2p24 and 12q13-q14 chromosomal regions. Based on the copy number array data, we sublocalized the minimum common regions of 2p24 and 12q13-q14 amplification to a 0.83 Mb region containing the DDX1 and MYCN genes, and a 0.55 Mb region containing 27 genes, respectively. Using fluorescent in situ hybridization assays to measure copy number of the 2p24 and 12q13-q14 regions in over 100 cases, we detected these amplicons in 13% and 12% of cases, respectively. Comparison with fusion status revealed that 2p24 amplification occurred preferentially in cases positive for PAX3-FOXO1 or PAX7-FOXO1 while 12q13-q14 amplification occurred preferentially in PAX3-FOXO1-positive cases. Expression studies demonstrated that MYCN was usually overexpressed in cases with 2p24 amplification while multiple genes were overexpressed in cases with 12q13-q14 amplification. Finally, although 2p24 amplification did not have a significant association with clinical outcome, 12q13-q14 amplification was associated with significantly worse failure-free and overall survival that was independent of gene fusion status.

Original languageEnglish (US)
Pages (from-to)661-672
Number of pages12
JournalGenes Chromosomes and Cancer
Volume48
Issue number8
DOIs
StatePublished - Aug 1 2009

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Alveolar Rhabdomyosarcoma
Genes
Genetic Translocation
Genetic Heterogeneity
Gene Fusion
Oligonucleotide Array Sequence Analysis
Fluorescence In Situ Hybridization
Skeletal Muscle
Pediatrics
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma : A report from the children's oncology group. / Barr, Frederic G.; Duan, Fenghai; Smith, Lynette M; Gustafson, Donna; Pitts, Mandy; Hammond, Sue; Gastier-Foster, Julie M.

In: Genes Chromosomes and Cancer, Vol. 48, No. 8, 01.08.2009, p. 661-672.

Research output: Contribution to journalArticle

Barr, Frederic G. ; Duan, Fenghai ; Smith, Lynette M ; Gustafson, Donna ; Pitts, Mandy ; Hammond, Sue ; Gastier-Foster, Julie M. / Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma : A report from the children's oncology group. In: Genes Chromosomes and Cancer. 2009 ; Vol. 48, No. 8. pp. 661-672.
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