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.
%0 Journal Article
%1 Vater.2009
%A Vater, Inga
%A Wagner, Florian
%A Kreuz, Markus
%A Berger, Hilmar
%A Martín-Subero, José I.
%A Pott, Christiane
%A Martinez-Climent, Jose A.
%A Klapper, Wolfram
%A Krause, Kristina
%A Dyer, Martin J S,
%A Gesk, Stefan
%A Harder, Lana
%A Zamo, Alberto
%A Dreyling, Martin
%A Hasenclever, Dirk
%A Arnold, Norbert
%A Siebert, Reiner
%D 2009
%J British journal of haematology
%K Cell_Line,_Tumor Chromosome_Aberrations Chromosomes,_Human,_Pair_11 Chromosomes,_Human,_Pair_14 Gene_Amplification Gene_Deletion Gene_Expression_Profiling/methods Genomics Humans In_Situ_Hybridization,_Fluorescence Loss_of_Heterozygosity Lymphoma,_Mantle-Cell/genetics Microtubule-Associated_Proteins/genetics Oligonucleotide_Array_Sequence_Analysis Translocation,_Genetic Uniparental_Disomy
%N 3
%P 317–331
%T GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma
%V 144
%X 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.
@article{Vater.2009,
abstract = {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.},
added-at = {2014-10-15T15:04:29.000+0200},
author = {Vater, Inga and Wagner, Florian and Kreuz, Markus and Berger, Hilmar and Martín-Subero, José I. and Pott, Christiane and Martinez-Climent, Jose A. and Klapper, Wolfram and Krause, Kristina and {Dyer, Martin J S} and Gesk, Stefan and Harder, Lana and Zamo, Alberto and Dreyling, Martin and Hasenclever, Dirk and Arnold, Norbert and Siebert, Reiner},
biburl = {https://www.bibsonomy.org/bibtex/26cee292f694cd6ccc530f0a180eaad94/drtester},
interhash = {0fed238bc7a9a12321ce11fcbcf3c9aa},
intrahash = {6cee292f694cd6ccc530f0a180eaad94},
journal = {British journal of haematology},
keywords = {Cell_Line,_Tumor Chromosome_Aberrations Chromosomes,_Human,_Pair_11 Chromosomes,_Human,_Pair_14 Gene_Amplification Gene_Deletion Gene_Expression_Profiling/methods Genomics Humans In_Situ_Hybridization,_Fluorescence Loss_of_Heterozygosity Lymphoma,_Mantle-Cell/genetics Microtubule-Associated_Proteins/genetics Oligonucleotide_Array_Sequence_Analysis Translocation,_Genetic Uniparental_Disomy},
number = 3,
pages = {317–331},
timestamp = {2014-10-15T15:04:29.000+0200},
title = {GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma},
volume = 144,
year = 2009
}