Extra copies of ALK gene locus is a recurrent genetic aberration and favorable prognostic factor in both ALK-positive and ALK-negative anaplastic large cell lymphomas

Abstract

Systemic anaplastic large cell lymphoma (ALCL) is subtyped into ALK-positive ALCL and ALK-negative ALCL based on the presence or absence of ALK protein expression. ALK-positive ALCL is characterized by t(2;5)(p23;q35)/NPM-ALK or variant ALK-involved translocations, while little is known about the genetic changes in ALK-negative ALCL. We investigated the structural and numerical aberrations of the ALK gene using interphase fluorescence in situ hybridization (FISH) in 81 cases with ALCL and analyzed their association with clinical outcome of the patients. ALK gene rearrangement was found in 47 of 50 (94%) ALK-positive ALCLs but in none of 31 ALK-negative ALCLs. Extra copies of the ALK gene locus, representing mainly extra copies of chromosome 2, were seen in 19 ALK-positive (38%) and 15 ALK-negative (48%) cases (P=0.357). In 55 cases with follow-up information, the mean survival time of the 38 ALK positive cases (58months) was significantly longer than that of 17 ALK-negative cases (22.5months) (P=0.038). Interestingly, the cases with extra copies of ALK had a significantly longer mean survival time than those without (64.4months vs 35.3months) (P=0.023) and this difference was observed in both ALK-positive (72.3 vs 45.9months) and ALK-negative (34.7 vs 9.9months) cases. Multivariate analysis showed that both ALK protein expression and extra copies of ALK gene were independent predictors for better survival (P=0.008). Our results suggest that the extra copies of ALK gene locus are a frequent genetic aberration in both ALK-positive and ALK-negative ALCL and is a favorable prognostic marker for the patients.