Expression of centrosome-associated gene products is linked to tetraploidization in mantle cell lymphoma

Abstract

In mantle cell lymphoma (MCL), a blastoid variant with a striking tendency to harbor chromosome numbers in the tetraploid range has been identified. Centrosome aberrations have recently been implicated in the induction of aneuploidy in many human malignancies including MCL by malsegregation of chromosomes during anaphase of mitosis. Recently, we showed that centrosome aberrations occur more frequently in tetraploid MCL as compared to their diploid counterparts. To test the hypothesis of an association between tetraploidization and expression of genes coding for centrosomal proteins in MCL, tumor RNA of 33 MCL samples was hybridized to custom-made cDNA microarrays, representing 4,628 distinct human gene-specific fragments, with particular enrichment for cancer-relevant (n = 2,440) and centrosome-associated genes (n = 359). Notably, 4 of the 6 most significant genes (CAMKK2, PCNT2, TUBGCP3, TUBGCP4) discriminating between diploid and near-tetraploid MCL code for centrosomal proteins. As confirmed by quantitative RT-PCR analysis, calcium/calmodulin-dependent protein kinase II (CAMKK2), pericentrin (PCNT2) and gamma-tubulin complex associated protein 3 (TUBGCP3) were all found to be significantly higher expressed in near-tetraploid than in diploid MCL samples. In conclusion, we describe a comprehensive expression signature of a set of genes associated with tetraploidization in MCL. The high expression level of centrosome-associated gene products in blastoid MCL matches the description of more frequent centrosome aberrations in this MCL variant.