Gene expression and copy number profiling of follicular lymphoma biopsies from patients treated with first-line rituximab without chemotherapy

Abstract

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/– interferon).

Keywords:

• Follicular lymphoma
• whole genome microarrays
• gene expression profiling
• copy number profiling
• cox models

Acknowledgements

We would like to thank all the patients and all collaborative investigators and research nurses from the Nordic Lymphoma Group (NLG) and Inge Klier for technical assistance.

Disclosure statement

This work was supported by F. Hoffmann-La Roche Ltd (research funding paid to the Institute of Pathology, University of Würzburg (chair: A.R.) and the Nordic Lymphoma Group, funding for two investigator-initiated clinical trials (E.K.))

Data availability statement

The GE and SNP6.0 CN data cohort have been deposited at the European Genome-phenome Archive (EGA; http://www.ebi.ac.uk/ega/) under accession number EGAS00001002566.