Concurrent disruption of cell cycle associated genes in mantle cell lymphoma : a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

• Published in: Leukemia Vol. 12; no. 8; pp. 1266 - 1271
• Main Authors: GRØNBAEK, K, NEDERGAARD, T, ANDERSEN, M. K, THOR STRATEN, P, GULDBERG, P, MØLLER, P, ZEUTHEN, J, EBBE HANSEN, N, HOU-JENSEN, K, RALFKIAER, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.08.1998; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cancer; Cell cycle; Cell Cycle Proteins; Cyclin D1; Cyclin D1 - metabolism; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-Dependent Kinases - metabolism; Female; Gene deletion; Genes; Genes, cdc; Genotype; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, Non-Hodgkin - genetics; Male; Mantle cell lymphoma; Medical sciences; Middle Aged; Mutation; Neoplasia; Neoplasms; p53 Protein; Pathogenesis; Phenotype; Point mutation; Proto-Oncogene Proteins; Retina; Retinoblastoma; Retinoblastoma protein; Retinoblastoma Protein - metabolism; Transcription Factors - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins; Tumors; Human; Cell proliferation; Retinoblastoma gene; Gene overexpression; Malignant hemopathy; B-Lymphocyte; Non Hodgkin lymphoma; Gene expression; Cyclin D1; Cyclin dependent kinase inhibitor; TP53 Gene; Lymphoproliferative syndrome; Cell cycle; Mantle cell lymphoma; Point mutation; Deletion; Genetics; Methylation; Tumor suppressor gene
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401090

Mantle cell lymphomas (MCL) are morphologically and immunophenotypically distinctive lymphoid neoplasms characterised by overexpression of cyclin D1. Recent studies have suggested that co-operating aberrations of cell cycle associated genes may provide a growth advantage to a tumour. To address this issue further, we investigated five typical and three aggressive (blastoid) MCL for alterations in the cell cycle regulating genes p15, p16, CDK4, Rb and p53. In 3/3 aggressive cases with cyclin D1 overexpression we found aberration of at least one additional gene. One case showed diminished expression of the retinoblastoma protein (pRb); one case harboured deletion of both p15 and p16; and one case exhibited both deletion of p16 and point mutation of p53. However, we also identified two typical cases which in addition to cyclin D1 overexpression exhibited diminished pRb expression and p15 and p16 hypermethylation, respectively. Our findings confirm and extend other recent investigations and indicate that co-operating genetic alterations of cell cycle-associated genes may contribute to the pathogenesis of MCL.