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. 2011 Nov;155(4):477-86.
doi: 10.1111/j.1365-2141.2011.08883.x. Epub 2011 Oct 8.

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  1 , 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
Affiliations

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 et al. Br J Haematol. 2011 Nov.

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.

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Figures

Figure 1
Figure 1
Summary of copy number gains and losses. Gains are indicated by the bars to the right of each chromosome, and losses are shown to the left. The thicker bars indicate areas of recurrent change.
Figure 2
Figure 2
Alignments are shown for recurrent gain of chromosome 1q (A), recurrent loss of chromosome 17p (B), and recurrent gain of chromosome 13q (C). D shows the probe distribution and gain amplitude for the three samples with 13q31 gain.
Figure 3
Figure 3
Relative expression of MIR17 miRNA is higher in samples with 13q31 gain. (A) Expression was measured by RT-PCR and is expressed as a ratio of mature miRNA control RNU6-2 expression for each sample. The samples with 13q31 MIR17HG locus gain are indicated by the cross-hatched fill. Results are the mean of two experiments from separate reverse transcription reactions normalized to expression levels from an FFPE spleen specimen. (B) The mean expression of MIR17 miRNA is significantly higher in samples with gain of 13q31; *p=0.043, t-test.
Figure 4
Figure 4
Comparison of relative expression of MYC and MIR17. The relative expression level of MIR17 is plotted for each sample as a function of the relative level of MYC, and there is no significant correlation.
See this image and copyright information in PMC

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