Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas
| Autor: | Chris De Wolf-Peeters, Iwona Wlodarska, Gregor Verhoef, Daan Dierickx, Helena Pospisilova, Katrien Van Roosbroeck, Peter Vandenberghe, José Thomas, Vera Vanhentenrijk, Francesca Minnei |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cyclin E Cyclin D Immunology Lymphoma Mantle-Cell Biology Blastoid Biochemistry Translocation Genetic Cyclin D1 Cyclin D2 Cyclins hemic and lymphatic diseases medicine Humans Cyclin D3 In Situ Hybridization Fluorescence Aged Cyclin Chromosomes Human Pair 14 Oncogene Proteins N-Myc Proto-Oncogene Protein Reverse Transcriptase Polymerase Chain Reaction Chromosomes Human Pair 11 Gene Expression Profiling Genetic Variation Nuclear Proteins Cell Biology Hematology Middle Aged medicine.disease biology.organism_classification Immunohistochemistry Molecular biology Gene Expression Regulation Neoplastic biology.protein Female Mantle cell lymphoma |
| Zdroj: | Blood. 111:5683-5690 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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