title: GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma.
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.
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel, Kiel, Germany. ivater@medgen.uni-kiel.de
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Hilmar
authors.initials: H
authors.lastname: Berger
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martinez-Climent
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Kristina
authors.initials: K
authors.lastname: Krause
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamo
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Dirk
authors.initials: D
authors.lastname: Hasenclever
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: 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
chemical_list: D008869:Microtubule-Associated Proteins