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Staiger, Annette M.; Hoster, Eva; Jurinovic, Vindi; Winter, Stefan; Leich, Ellen; Kalla, Claudia; Möller, Peter; Bernd, Heinz-Wolfram; Feller, Alfred C.; Koch, Karoline; Klapper, Wolfram; Stein, Harald; Hansmann, Martin-Leo; Hartmann, Sylvia; Dreyling, Martin; Weigert, Oliver; Hiddemann, Wolfgang; Herfarth, Klaus; Rosenwald, Andreas; Engelhard, Marianne; Ott, German; Horn, Heike (2020): Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles. In: Blood, Vol. 135, No. 3: pp. 181-190
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The genetic background of follicular lymphomas (FLs) diagnosed in advanced clinical stages III/IV, and which are frequently characterized by t(14;18), has been substantially unraveled. Molecular features, as exemplified in the clinicogenetic risk model m7FLIPI, are important tools in risk stratification. In contrast, little information is available concerning localized-stage FL (clinical stages I/II), which accounts for ∼20% of newly diagnosed FL in which the detection rate of t(14;18) is only ∼50%. To investigate the genetic background of localized-stage FL, patient cohorts with advanced-stage FL or localized-stage FL, uniformly treated within phase 3 trials of the German Low-Grade Lymphoma Study Group, were comparatively analyzed. Targeted gene expression (GE) profiling of 184 genes using nCounter technology was performed in 110 localized-stage and 556 advanced-stage FL patients. By penalized Cox regression, a prognostic GE signature could not be identified in patients with advanced-stage FL, consistent with results from global tests and univariate regression. In contrast, it was possible to define robust GE signatures discriminating localized-stage and advanced-stage FL (area under the curve, 0.98) by penalized logistic regression. Of note, 3% of samples harboring an \textquotedbladvanced-stage signature\textquotedbl in the localized-stage cohort exhibited inferior failure-free survival (hazard ratio HR, 7.1; P = .0003). Likewise, in the advanced-stage cohort, 7{\%} of samples with a {\textquotedbl}localized-stage signature{\textquotedbl} had prolonged failure-free survival (HR, 2.3; P = .017) and overall survival (HR, 3.4; P = .072). These data support the concept of a biological difference between localized-stage and advanced-stage FL that might contribute to the superior outcome of localized FL.