GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma.
The translocation t(11;14)(q13;q32) is the genetic hallmark of mantle cell lymphoma (MCL) but is not sufficient for inducing lymphomagenesis. Here we performed genome-wide 100K GeneChip Mapping in 26 t(11;14)-positive MCL and six MCL cell lines. Partial uniparental disomy (pUPD) was shown to be a recurrent chromosomal event not only in MCL cell lines but also in primary MCL. Remarkably, pUPD affected recurrent targets of deletion like 11q, 13q and 17p. Moreover, we identified 12 novel regions of recurrent gain and loss as well as 12 high-level amplifications and eight homozygously deleted regions hitherto undescribed in MCL. Interestingly, GeneChip analyses identified different genes, encoding proteins involved in microtubule dynamics, such as MAP2, MAP6 and TP53, as targets for chromosomal aberration in MCL. Further investigation, including mutation analyses, fluorescence in situ hybridisation as well as epigenetic and expression studies, revealed additional aberrations frequently affecting these genes. In total, 19 of 20 MCL cases, which were subjected to genetic and epigenetic analyses, and five of six MCL cell lines harboured at least one aberration in MAP2, MAP6 or TP53. These findings provide evidence that alterations of microtubule dynamics might be one of the critical events in MCL lymphomagenesis contributing to chromosomal instability.
Vater
Inga
I
Institute of Human Genetics, Christian-Albrechts University Kiel, Kiel, Germany. ivater@medgen.uni-kiel.de
Wagner
Florian
F
Kreuz
Markus
M
Berger
Hilmar
H
Martín-Subero
José I
JI
Pott
Christiane
C
Martinez-Climent
Jose A
JA
Klapper
Wolfram
W
Krause
Kristina
K
Dyer
Martin J S
MJ
Gesk
Stefan
S
Harder
Lana
L
Zamo
Alberto
A
Dreyling
Martin
M
Hasenclever
Dirk
D
Arnold
Norbert
N
Siebert
Reiner
R
D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005784:Gene Amplification; D017353:Gene Deletion; D020869:Gene Expression Profiling / Q000379:methods*; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014178:Translocation, Genetic; D024182:Uniparental Disomy
D008869:Microtubule-Associated Proteins