Comprehensive analysis of copy number and allele status identifies multiple chromosome defects underlying follicular...

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 or -extrinsic factors. FL carries the hallmark chromosomal translocation t(14;18), deregulating the expression of Bcl-2, but this is not sufficient to explain either FL biology or clinical behavior.

We have employed high-density genomic profiling technology using the Affymetrix 50K-XbaI oligonucleotide single nucleotide polymorphism-chip platform to interrogate the genomes of 58 fluorescence-activated cell-sorted (FACS) FL specimens for chromosomal copy number changes and 46 specimens for loss of heterozygosity (LOH).

We report (a) previously unknown high-frequency copy-neutral LOH (uniparental disomy) in FL on chromosomes 1p (approximately 50%) and 6p (approximately 30%); (b) that del6q is complex, as reported, with at least two regions of minimal common loss at 6q13-15 and 6q23-24, and that in addition, approximately 8% of FL specimens contain a homozygous deletion at 6q23.3-24.1 that spans the negative NFkappaB regulator A20 and the p53 apoptosis effector PERP; (c) that combined analysis of chromosome 17p for LOH, copy number, and p53 mutations shows that most p53 mutations in FL do not involve del17p. Finally, we map high-frequency LOH with and without copy loss on chromosomes 9p, 10q, and 16p and genomic gains on 2p15-16 and 8q24.22-24.3.

This comprehensive description of the pathologic anatomy of the FL genome uncovers novel genetic lesions and should aid with identification of genes relevant to FL biology and clinical behavior.