Array CGH Analysis for Target Genes at 6p21 Amplification Region in Diffuse Large B-Cell Lymphoma.

Amplification of 6p21 has been detected in various solid tumor and hematological neoplasms. These include hepatoma, osteosarcoma, pancreatic cancer, bladder cancer, and mantle cell lymphoma . However, no candidate target genes in this amplified region have been identified. In diffuse large B-cell lymphoma (DLBCL), no amplification has been reported. Recently, we established genome-wide array comparative genomic hybridization (array CGH) consisting of 2300 BAC clones that can survey a whole genome at the density of an average size of 1.3 Mb. The array CGH detected amplification at 6p21 in 12 of 70 (24%) DLBCL patients (Tagawa et al., Cancer Res. in press) and one DLBCL cell line, SUDHL-9. We next made high density array glass for 6p21 region with 23 BAC clones covering 3 Mb. We found that the minimal common region of amplification was approximately 2Mb in size. In this region, there are 27 known genes including cyclin D3. The cyclin D3 has been reported to be overexpressed in a case of DLBCL with t(6;14)(p21.1;q32.3). We have analyzed expression level of those genes in the minimal common region of amplification, and found that five genes, BYSL, cyclin D3, TBN, KIAA0240, and TBCC were overexpressed. These results indicate that not only cyclin D3 but also other genes are also possible target genes for the 6p21 amplification.