Genome Wide Analysis of Burkitt Lymphoma and Lymphomas Intermediate between Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma by Single Nucleotide Polymorphism Array
JF Gradowski, B Van Oss, U Chandran, L Finn, E Jacob, SH Swerdlow. University of Pittsburgh Medical School, Pittsburgh, PA; University of Pittsburgh Medical Center, Pittsburgh, PA; Seattle Children's Hospital, Seattle, WA
Background: The distinction of Burkitt lymphoma (BL) from other B-cell lymphomas with high grade features (HGL) can be very difficult. The 2008 WHO classification recognizes lymphomas with features intermediate between BL and diffuse large B-cell lymphomas and gene profiling studies have also reported "intermediate" cases. One major difference between the 2 groups is reported to be the "MYC" simple cytogenetic features in BL vs more complex abnormalities in HGL. The HGL remain to be better defined. SNP analysis allows for investigation of very small copy number variations (CNV) and uniparental disomies (UPD).
Design: 8 classical childhood BL cases and 14 adult HGL, plus 9 unpaired control normal frozen kidney samples were hybridized to the Affymetrix Human Mapping 250K Sty array. Copy number was analyzed in Partek 6.5 β. 3 BL and 4 HGL with SNP call rates of <86% were excluded. The genomic segmentation algorithm was performed and regions of gain and loss were identified. Normal variation was removed. Chi-square analysis was performed. UPD was analyzed in CNAG.
Results: Overall, cases showed 97.7±90.3 gains and 64.4±25.2 losses. There was no statistical difference in overall karyotypic complexity between BL and HGL; however, BL had significantly more deletions. Unsupervised principal component analysis based on calculated CNV separated the BL from most HGL.
Supervised clustering based on the 20 CNV with the lowest p values showed distinct separation of BL from HGL. UPD of multiple chromosomes was seen in 1 HGL.
Conclusions: This SNP analysis shows that sporadic BL cases are significantly more cytogenetically complex than previously thought. SNP array profiling demonstrates differences between the BL and many of the lymphomas intermediate between BL and DLBCL. As with the gene expression data, some intermediate cases have features more like BL than others. Further studies to confirm and validate these observations are required.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 178, Wednesday Morning