title: Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.
abstract: The genetics of t(11;14)(q13;q32)/cyclin D1-negative mantle cell lymphoma (MCL) is poorly understood. We report here 8 MCL cases lacking t(11;14) or variant CCND1 rearrangement that showed expression of cyclin D1 (2 cases), D2 (2 cases), and D3 (3 cases). One case was cyclin D negative. Cytogenetics and fluorescence in situ hybridization detected t(2;12)(p11;p13)/IGK-CCND2 in one of the cyclin D2-positive cases and t(6;14)(p21;q32)/IGH-CCND3 in one of the cyclin D3-positive cases. Moreover, we identified a novel cryptic t(2;14)(p24;q32) targeting MYCN in 2 blastoid MCLs: one negative for cyclin D and one expressing cyclin D3. Interestingly, both cases showed expression of cyclin E. Notably, all 3 blastoid MCLs showed a monoallelic deletion of RB1 associated with a lack of expression of RB1 protein and monoallelic loss of p16. In sum-mary, this study confirms frequent aberrant expression of cyclin D2 and D3 in t(11;14)-negative MCLs and shows a t(11;14)-independent expression of cy-clin D1 in 25% of present cases. Novel findings include cyclin E expression in 2 t(11;14)-negative MCLs characterized by a cryptic t(2;14)(p24;q32) and identification of MYCN as a new lymphoma oncogene associated with a blastoid MCL. Clinically important is a predisposition of t(11;14)-negative MCLs to the central nervous system involvement.
authors.affiliation: Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium. iwona.wlodarska@uz.kuleuven.ac.be
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Daan
authors.initials: D
authors.lastname: Dierickx
authors.forename: Vera
authors.initials: V
authors.lastname: Vanhentenrijk
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Roosbroeck
authors.forename: Helena
authors.initials: H
authors.lastname: Pospísilová
authors.forename: Francesca
authors.initials: F
authors.lastname: Minnei
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: José
authors.initials: J
authors.lastname: Thomas
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Chris
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000328:Adult; D000368:Aged; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins