Genomic alterations important for the prognosis in patients with follicular lymphoma treated in SWOG study S0016

Abstract

Although recent advances in molecular genetics have enabled improved risk classification of follicular lymphoma (FL) using, for example, the m7-FLIPI score, the impact on treatment has been limited. We aimed to assess the prognostic significance of copy-number aberrations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) identified by chromosome genomic-Array testing (CGAT) at FL diagnosis using prospectively collected clinical trial specimens from 255 patients enrolled in the SWOG study S0016. The impact of genomic aberrations was assessed for early progression (progressed or died within 2 years after registration), progression-free survival (PFS), and overall survival (OS). We showed that increased genomic complexity (ie, the total number of aberration calls) was associated with poor outcome in FL. Certain chromosome arms were critical for clinical outcome. Prognostic CNAs/cnLOH were identified: whereas early progression was correlated with 2p gain (P5.007; odds ratio [OR]52.55 [1.29, 5.03]) and 2p cnLOH (P5.005; OR510.9 [2.08, 57.2]), 2p gain specifically encompassing VRK2 and FANCL predicted PFS (P 5 .01; hazard ratio51.80 [1.14, 2.68]) as well as OS (P5.005; 2.40 [1.30, 4.40]); CDKN2A/B (9p) deletion correlated with worse PFS (P 5 .004, 3.50 [1.51, 8.28]); whereas CREBBP (16p) (P < .001; 6.70 [2.52, 17.58]) and TP53 (17p) (P