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Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic

Karen E Deffenbacher1, Javeed Iqbal, Warren Sanger

  • 1Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198-3135, USA.

Blood
|March 1, 2012
PubMed

Insights

Pediatric diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) are distinct entities, despite similar treatment and outcomes in children. Gene expression profiling revealed unique molecular signatures and chromosomal abnormalities in pediatric DLBCL, suggesting novel therapeutic targets.

Area of Science:

  • Hematology
  • Pediatric Oncology
  • Molecular Biology

Background:

  • Burkitt lymphoma (BL) is common in children, while diffuse large B-cell lymphoma (DLBCL) is rare.
  • Pediatric BL and DLBCL share similar treatment protocols and exhibit better outcomes in children than adults.
  • Distinct molecular profiles differentiate pediatric DLBCL from BL, despite overlapping clinical presentations.

Purpose of the Study:

  • To molecularly characterize pediatric DLBCL and compare it with adult DLBCL and pediatric BL.
  • To identify genetic alterations and pathway differences that distinguish pediatric B-cell lymphomas.
  • To explore potential novel therapeutic targets for pediatric B-cell non-Hodgkin lymphoma.

Main Methods:

  • Gene expression profiling (GEP) and miRNA expression profiling were used to cluster pediatric and adult lymphoma samples.
  • Pathway analysis of GEP data was performed to identify molecular differences.
  • Array-based comparative genomic hybridization (CGH) was employed to detect chromosomal abnormalities.

Main Results:

  • GEP and miRNA profiling clearly separated pediatric DLBCL from BL into distinct clusters.
  • Pediatric DLBCL showed a predominance of the germinal center B-cell subtype (6:1 ratio).
  • Frequent 8q24 abnormalities, including MYC alterations, were observed in pediatric DLBCL (31% rearrangement, 50% gain/amplification).
  • MYC rearrangement was highly prevalent in BL (96%).
  • CGH analysis revealed shared and unique chromosomal abnormalities between pediatric and adult DLBCL, suggesting distinct pathogenetic mechanisms.

Conclusions:

  • Pediatric DLBCL and BL are molecularly distinct entities.
  • Pediatric DLBCL harbors unique genetic alterations, including MYC pathway involvement and specific chromosomal abnormalities.
  • These findings highlight age-related pathogenetic differences and suggest potential novel therapeutic targets for pediatric B-cell lymphomas.

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