Genomic Profiling of Follicular Lymphoma Identifies Novel High-Frequency Copy-Neutral Loss of Heterozygosity on Chromosomes 1p and 6p and Identifies Candidate Genes Involved in FL Biology.

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin’s lymphoma in the Western world. The clinical course is variable and only in part explained by known tumor-intrinsic (genetic) or -extrinsic (infiltrating immune cells, infiltrating macrophage content) factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior. We have employed genomic profiling technology using the Affymetrix 50K-Xba1 oligonucleotide single nucleotide polymorphism (SNP) chip platform to interrogate the genomes of 58 FL specimens for loss of heterozygosity (LOH) and chromosomal copy number changes. Where available, these high-density genomic data were correlated with published FL gene expression data. Using this integrated approach, we provide data that suggest that i) Bcl11A is a likely target gene for the amplification on chromosome 2p15–16 in FL, ii) that the amplification of der(18)t(14;18) does not include Bcl-2, iii) high-frequency copy-neutral LOH exists at 1p36 (50%) and 6p (33%), and that 6p LOH possibly deregulates IRF4 and, iv) deletion 6q is non-overlapping, complex and possibly involves four or more gene loci of importance. In addition, high-frequency LOH (with and without chromosomal copy loss) exists on chromosomes 9p, 10q and 16p. These data should facilitate analysis of specific genes in FL and should allow for development of a SNP -and genomics-based assay for FL risk stratification and outcome prognostication.