Systematic analysis of the frequently amplified 2p15-p16.1 locus reveals PAPOLG as a potential proto-oncogene in follicular and transformed follicular lymphoma

Abstract

Transformed follicular lymphoma (tFL) originates from histological transformation of follicular lymphoma (FL), which isthe most common indolent non-Hodgkin lymphoma. High-resolution genomic copy-number analysis previously identified frequentamplification of the 2p15-p16.1 locus in FL and tFL cases. The genes (i.e. BCL11A, PAPOLG, PUS10, and USP34) in this amplifiedlocus have not been systematically investigated to date in terms of their role in FL pathogenesis or transformation to tFL. Here weinvestigated the relationship between amplification and expression of genes in 2p15-p16.1 as well as their expression after histologicaltransformation. NCBI GEO SNP array and gene expression profile (GEP) data of tFL cases were analyzed to evaluate the relationshipbetween amplification and mRNA expression. Moreover, transcript levels of these four genes in FL cases were compared with thoseof patient-matched tFL cases and normal B-cells. Amplification of the 2p15-p16.1 locus is associated with increased transcription ofBCL11A and PAPOLG in tFL cases, of which the latter showed increased expression after histological transformation. Compared withthe level in normal B-cells, PAPOLG was significantly overexpressed in FL cases, but expression levels of the other three genes did notshow any significant difference. Altogether these results suggest that PAPOLG may be the most critical gene in terms of transformationto tFL.