Allelic genotyping reveals a hierarchy of genomic alterations in mantle cell lymphoma associated to cell proliferation

Abstract

Mantle cell lymphoma (MCL) is a distinct subentity of non-Hodgkin lymphoma, characterized by the chromosomal translocation t(11;14)(q13;q32) leading to an overexpression of cyclin D1 in virtually all cases. However, additional cytogenetic aberrations are apparent in the vast majority of MCL. Applying LOH analysis in 52 MCL patient samples, we confirmed frequent alterations in 9p21 (28.6%) and p53 (28.9%) but also detected allelic losses in 1p21, 9q21, 13q13-14, 13q31-32, 17p13.1, and 17p13.3 in 28-45% of cases and allelic gains in 3q27-28 and 19p13.3 in 14-22% of cases. In addition, losses in the 2p23 and 7q22-35 genomic regions not previously described to be altered in MCL were identified in up to 20% of cases. Applying multivariate analysis, a cluster of genomic aberrations including 1p21, 3q27, 7q22-36, 6p24, 9p21, 9q31, and 16p12 alterations was identified which was closely associated to cell proliferation as determined by Ki67 immunostaining. This proliferation-dependent network of oncogenic alterations complements the previously identified proliferation expression signature described by RNA expression profiling in MCL.

High‐resolution genomic screening in mantle cell lymphoma—specific changes correlate with genomic complexity, the proliferation signature and survival

“…On the other hand, the second cluster had an interesting pattern represented by the presence of 11q loss in all cases and at the same time complete absence of 13q loss, larger 8q gains, 3q gains, and 7p gains. This implies that some aberrations tend to occur together in MCL as a few studies have previously suggested (Sander et al, 2008;Hutter et al, 2009). However, the relatively small dataset available for this study was a limiting factor in the analysis, and therefore larger studies are required to clarify further the co-occurrence of various CNAs in MCL subgroups.…”