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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Oncología molecular > DA - CIMA - Oncología - Oncología molecular - Artículos de Revista >

GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma
Authors: Vater, I. (Inga)
Wagner, F. (Florian)
Kreuz, M. (Markus)
Berger, H. (H.)
Martin-Subero, J.I. (José Ignacio)
Pott, C. (Christiane)
Martinez-Climent, J.A. (José Angel)
Klapper, W. (W.)
Krause, K. (Kristina)
Dyer, M.J.S. (Martin J. S.)
Gesk, S. (Stefan)
Harder, L. (Lana)
Zamo, A. (Alberto)
Dreyling, M. (Martin)
Hasenclever, D. (D.)
Arnold, N. (N.)
Siebert, R. (Reiner)
Keywords: Mantle cell lymphoma
Microarray
Single nucleotide polymorphisms
Microtubule-associated proteins
Partial uniparental disomy
Issue Date: 2009
Publisher: Wiley-Blackwell
Publisher version: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2008.07443.x/abstract;jsessionid=BEFBDF14B458CCB432FC312E23B01150.d02t01
ISSN: 1365-2141
Citation: Vater I, Wagner F, Kreuz M, Berger H, Martin-Subero JI, Pott C, et al. GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma. Br J Haematol 2009 Feb;144(3):317-331.
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.
Permanent link: http://hdl.handle.net/10171/17890
Appears in Collections:DA - CIMA - Oncología - Oncología molecular - Artículos de Revista

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