title: Novel chromosomal imbalances in mantle cell lymphoma detected by genome-wide array-based comparative genomic hybridization.
abstract: Mantle cell lymphoma (MCL) is an aggressive, highly proliferative B-cell non-Hodgkin lymphoma, characterized by the specific t(11;14)(q13;q32) translocation. It is well established that this translocation alone is not sufficient to promote MCL development, but that additional genetic changes are essential for malignant transformation. We have identified such additional tumorigenic triggers in MCL tumors, by applying genome-wide array-based comparative genomic hybridization with an 800-kilobase (kb) resolution. This strategy, combined with a newly developed statistical approach, enabled us to confirm previously reported genomic alterations such as loss of 1p, 6q, 11q, 13q and gain of 3q and 8q, but it also facilitated the detection of novel recurrent genomic imbalances, such as gain of 4p12-13 and loss of 20p12.1-12.3, 20q12-13.2, 22q12.1-12.3, and 22q13.31-13.32. Genomic hotspot detection allowed for the identification of small genomic intervals that are frequently affected (57%-93%), resulting in interesting positional candidate genes such as KITLG, GPC5, and ING1. Finally, by assessing multiple biopsies from the same patient, we show that seemingly stable genomes do show subtle genomic changes over time. The follow-up of multiple biopsies of patients with MCL by high-resolution genomic profiling is expected to provide us with new clues regarding the relation between clinical outcome and in vivo cytogenetic evolution.
authors.affiliation: Department of Pathology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.schraders@pathol.umcn.nl
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Huub M P
authors.initials: HM
authors.lastname: Straatman
authors.forename: Irene M
authors.initials: IM
authors.lastname: Janssen
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Eric F P M
authors.initials: EF
authors.lastname: Schoenmakers
authors.forename: Johan H J M
authors.initials: JH
authors.lastname: van Krieken
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015894:Genome, Human; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods