Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH)

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is an aggressive extranodal B-cell non-Hodgkin's lymphoma with specific clinical, histopathological and genomic features. To characterize further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using arraybased comparative genomic hybridization (matrix-or array-CGH) to a 2.8k genomic microarray. Due to a higher genomic resolution, we identified altered chromosomal regions in much higher frequencies compared with standard CGH: for example,, þ 12q (30%) and þ 18q21 (24%). Moreover, previously unknown small interstitial chromosomal low copy number alterations (for example, À6p21, À11q13.3) and a total of 19 DNA amplifications were identified by array-CGH. For 17 chromosomal localizations (10 gains and 7 losses), which were altered in more than 10% of the analyzed cases, we delineated minimal consensus regions based on genomic base pair positions. These regions and selected immunohistochemistries point to candidate genes that are discussed in the context of NF-jB transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. Our data confirm the genomic uniqueness of this tumor and provide physically mapped genomic regions of interest for focused candidate gene analysis.

Practice guidelines for the management of extranodal non-Hodgkin's lymphomas of adult non-immunodeficient patients. Part I: primary lung and mediastinal lymphomas. A project of the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

“…[35][36][37] Using array-based comparative genomic hybridization, candidates genes were selected in the context of NF-κB transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. 38 These data confirm the genomic uniqueness of this tumor. PMLB-CL appears to be a distinct clinicopathological entity, characterized by locally invasive anterior mediastinal mass with notable aggressiveness.…”

Primary mediastinal B‐cell lymphoma

“…18 Common regions of loss are at 1p, 3p, 13q, 15q and 17p. 18,19 These patterns of genomic changes in PMBL are distinct from those observed in other subgroups of DLBCL that have been defined by transcription profiling. 20 …”

“…[16][17][18][19][20] By florescence in situ hybridization (FISH) analysis, genomic gains have been identified in 75% of cases at this loci. 19,29 There is good evidence for constitutive activation of NF-κB pathway in PMBL. PMBL cell line survival is critically dependent upon NF-κB, and the target gene profile of NF-κB in PMBL is clearly directed towards genes promoting cell survival and inhibiting apoptosis.…”

Microarray‐based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status

“…Array-CGH analysis was performed as described recently Hummel et al, 2006;Rü cker et al, 2006;Wessendorf et al, 2007). A detailed description of the chip production, DNA labeling, hybridization procedure, data acquisition, and validation of results is given in the supporting information.…”

“…Only those clones were selected for the chip where FISH mapping and sequence data were congruent. Furthermore, 1299 DNA fragments, which represent critical regions in B-cell neoplasms were added to the clone set (Hummel et al, 2006;Rü cker et al, 2006;Wessendorf et al, 2007). Megabasepairlocalization, clone names, chromosomal localizations, and aberrations are listed in Supplemental Table S1.…”