Genomic Profiling of Plasmablastic Lymphoma Using BAC Array CGH Revealing Significant Overlapping Genomic Lesions with DLBCL
J Taylor, W Huang, F Facchetti, E Jaffe, C Chang. The Methodist Hospital/TMHRI, Houston, TX; Chang-Gung Memorial Hospital, Taiwan; University of Brescia, Brescia, Italy; NCI/NIH, Bethesda, MD
Background: Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma (DLBCL). Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related) and PCM using array-based comparative genomic hybridization.
Design: Paraffin blocks of PL (n=16), DLBCL (AIDS-related n=13; non AIDS-related n=13) and PCM (n=8) were retrieved. One H&E section of each case was analyzed. DNA was extracted. Tumor DNA and control DNA was labeled with Cy5 or Cy3, hybridized to array slides and imaged using an Axon 4000B scanner and GenePix Pro 6.0 scanning software. Differences between the log base 2 median minus background values were used as raw data for analysis. After normalization, values for duplicated spots representing one clone were averaged. The top 75 clones showing highest degrees of gain or loss were selected for each case.
Results: Examination of genomic data in PL revealed that the most frequent segmental gain (> 40%) include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related) cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation.
Conclusions: To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 192, Monday Morning