Genome wide copy number analysis of paediatric Burkitt lymphoma using formalin-fixed tissues reveals a subset with gain of chromosome 13q and corresponding miRNA over expression

Joshua D. Schiffman, Patrick D. Lorimer, Vladimir Rodic, Mona S. Jahromi, Jonathan M. Downie, Michael G. Bayerl, Jennifer N Sanmann, Pamela A. Althof, Warren G. Sanger, Phillip Barnette, Sherrie L. Perkins, Rodney R. Miles

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The majority of paediatric Burkitt lymphoma (pBL) patients that relapse will die of disease, but markers for this high-risk subset are unknown. MYC translocations characterize pBL, but additional genetic changes may relate to prognosis and serve as potential biomarkers. We utilized a molecular inversion probe single nucleotide polymorphism assay to perform high resolution, genome-wide copy number analysis on archival formalin-fixed, paraffin-embedded pBL and germline tissues. We identified copy number abnormalities (CNAs) in 18/28 patients (64%) with a total of 62 CNAs that included 32 gains and 30 copy number losses. We identified seven recurrent CNAs including 1q gain (7/28, 25%), 13q gain (3/28, 11%), and 17p loss (4/28, 14%). The minimum common amplified region on 13q was at 13q31 and included the MIR17HG (MIR17-92) locus. Samples with this gain had higher levels of MIR17 RNA and showed a tendency for early relapse. Tumour-specific uniparental disomy was identified in 32% of cases and usually was recurrent. These results demonstrate that high-resolution copy number analysis can be performed on archival lymphoma tissue specimens, which has significance for the study of rare diseases.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalBritish Journal of Haematology
Volume155
Issue number4
DOIs
StatePublished - Nov 1 2011

Fingerprint

Burkitt Lymphoma
MicroRNAs
Formaldehyde
Chromosomes
Genome
Pediatrics
Uniparental Disomy
Recurrence
Molecular Probes
Rare Diseases
Paraffin
Single Nucleotide Polymorphism
Lymphoma
Biomarkers
RNA
Neoplasms

Keywords

  • Chromosome 13q
  • Copy number analysis
  • Formalin-fixed - paraffin-embedded
  • MIR17HG
  • Molecular inversion probes
  • Paediatric Burkitt lymphoma

ASJC Scopus subject areas

  • Hematology

Cite this

Genome wide copy number analysis of paediatric Burkitt lymphoma using formalin-fixed tissues reveals a subset with gain of chromosome 13q and corresponding miRNA over expression. / Schiffman, Joshua D.; Lorimer, Patrick D.; Rodic, Vladimir; Jahromi, Mona S.; Downie, Jonathan M.; Bayerl, Michael G.; Sanmann, Jennifer N; Althof, Pamela A.; Sanger, Warren G.; Barnette, Phillip; Perkins, Sherrie L.; Miles, Rodney R.

In: British Journal of Haematology, Vol. 155, No. 4, 01.11.2011, p. 477-486.

Research output: Contribution to journalArticle

Schiffman, Joshua D. ; Lorimer, Patrick D. ; Rodic, Vladimir ; Jahromi, Mona S. ; Downie, Jonathan M. ; Bayerl, Michael G. ; Sanmann, Jennifer N ; Althof, Pamela A. ; Sanger, Warren G. ; Barnette, Phillip ; Perkins, Sherrie L. ; Miles, Rodney R. / Genome wide copy number analysis of paediatric Burkitt lymphoma using formalin-fixed tissues reveals a subset with gain of chromosome 13q and corresponding miRNA over expression. In: British Journal of Haematology. 2011 ; Vol. 155, No. 4. pp. 477-486.
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AU - Lorimer, Patrick D.

AU - Rodic, Vladimir

AU - Jahromi, Mona S.

AU - Downie, Jonathan M.

AU - Bayerl, Michael G.

AU - Sanmann, Jennifer N

AU - Althof, Pamela A.

AU - Sanger, Warren G.

AU - Barnette, Phillip

AU - Perkins, Sherrie L.

AU - Miles, Rodney R.

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AB - The majority of paediatric Burkitt lymphoma (pBL) patients that relapse will die of disease, but markers for this high-risk subset are unknown. MYC translocations characterize pBL, but additional genetic changes may relate to prognosis and serve as potential biomarkers. We utilized a molecular inversion probe single nucleotide polymorphism assay to perform high resolution, genome-wide copy number analysis on archival formalin-fixed, paraffin-embedded pBL and germline tissues. We identified copy number abnormalities (CNAs) in 18/28 patients (64%) with a total of 62 CNAs that included 32 gains and 30 copy number losses. We identified seven recurrent CNAs including 1q gain (7/28, 25%), 13q gain (3/28, 11%), and 17p loss (4/28, 14%). The minimum common amplified region on 13q was at 13q31 and included the MIR17HG (MIR17-92) locus. Samples with this gain had higher levels of MIR17 RNA and showed a tendency for early relapse. Tumour-specific uniparental disomy was identified in 32% of cases and usually was recurrent. These results demonstrate that high-resolution copy number analysis can be performed on archival lymphoma tissue specimens, which has significance for the study of rare diseases.

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