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GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma
Author(s) -
Vater Inga,
Wagner Florian,
Kreuz Markus,
Berger Hilmar,
MartínSubero José I.,
Pott Christiane,
MartinezCliment Jose A.,
Klapper Wolfram,
Krause Kristina,
Dyer Martin J. S.,
Gesk Stefan,
Harder Lana,
Zamo Alberto,
Dreyling Martin,
Hasenclever Dirk,
Arnold Norbert,
Siebert Reiner
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07443.x
Subject(s) - biology , mantle cell lymphoma , chromosome instability , chromosomal translocation , epigenetics , cancer research , genetics , genome instability , uniparental disomy , gene , lymphoma , comparative genomic hybridization , microbiology and biotechnology , genome , karyotype , chromosome , dna damage , immunology , dna
Summary 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.