Single Nucleotide Polymorphism Array (SNP-A) Analysis of EBV+ and EBV- Monomorphic B-Cell Post-Transplant Lymphoproliferative Disorders (M-B-PTLD)
SE Gibson, MA Nalesnik, BP Nelson, AM Evens, SH Swerdlow. University of Pittsburgh School of Medicine, Pittsburgh, PA; Northwestern University Feinberg School of Medicine, Chicago, IL
Background: M-B-PTLD are heterogeneous and include EBV+ and EBV- cases with most cases resembling diffuse large B-cell lymphoma (DLBCL) or less often Burkitt lymphoma (BL), or a plasma cell neoplasm. SNP-A analysis allows identification of small, previously unrecognized, chromosomal alterations that may help further our understanding of PTLD.
Design: 10 paraffin-embedded M-B-PTLD (8 DLBCL, 1 BL and 1 lymphoma with features intermediate between DLBCL and BL) and 9 unpaired frozen kidney controls were studied with the Affymetrix 250K Sty SNP-A. Data was analyzed using CNAG and Partek 6.5. Abnormalities of <10,000 bp were excluded from further analysis. All cases were stained for CD10, BCL-6, IRF4 and EBER-ISH.
Results: 4/10 cases were EBER+ and 5/10 had a germinal center (GC) phenotype. Overall, there were more chromosomal gains (1369) than deletions (643). Gains (12,005 – 265,252 bp) were most common at 1q42.11, 7q31.1, 10q26.13, 11q24.3, 12p13.31, 12q13.2, and 18q11.2. High-level amplifications were most common at 7p22.3-21.2 and 12p13.1. Deletions (37603 – 95870 bp) were most common at 2q14.3, 5q13.3, and 5q35.2. Uniparental disomies (UPD) were only found in 2 cases. EBV+ vs. EBV- M-B-PTLD could be distinguished with supervised hierarchical clustering (36 abnormalities, p ≤ 0.04).
EBV+ cases had more numerous chromosomal deletions (2p24.1, 4p15.1, 8p23.1 and 10q21.2; p ≤ 0.01) while EBV- cases had more numerous chromosomal gains (1p32.1, 6q16.2, 7p13, 14q24.2 and 18q21.2; p ≤ 0.01). Supervised hierarchical clustering with 1 overlapping and 30 distinct abnormalities distinguished GC from non-GC cases (p ≤ 0.04). Unsupervised clustering did not distinguish any of these groups.
Conclusions: SNP-A analysis shows many recurrent chromosomal alterations in M-B-PTLD. Chromosomal gains were more frequent than deletions and UPD occurred, but was not common. A small number of non-overlapping chromosomal abnormalities appear to distinguish EBV+ vs. EBV- and GC vs. non-GC M-B-PTLD. Validation and investigation of the altered regions can further elucidate our understanding of PTLD.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 181, Monday Morning