Deletion of Cyclin-Dependent Kinase 4 Inhibitor Genes P15 and P16 in Non-Hodgkin's Lymphoma

• Published in: Blood 1995-10, Vol.86 (8), p.2900-2905
• Main Authors: Koduru, P.R.K., Zariwala, M., Soni, M., Gong, J.Z., Xiong, Y., Broome, J.D.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Cell Cycle Proteins; Chromosomes, Human, Pair 11 - ultrastructure; Chromosomes, Human, Pair 18 - ultrastructure; Chromosomes, Human, Pair 3 - ultrastructure; Chromosomes, Human, Pair 8 - ultrastructure; Chromosomes, Human, Pair 9 - ultrastructure; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; Cyclin-Dependent Kinases - antagonists & inhibitors; Enzyme Inhibitors; Female; Gene Deletion; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - genetics; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Neoplasm Proteins - genetics; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proto-Oncogene Proteins; Proto-Oncogenes; Translocation, Genetic; Tumor Suppressor Proteins
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.8.2900.2900

B-cell non-Hodgkin's lymphoma (NHL) is a heterogeneous lymphoid malignancy consisting of several histologic types. Alterations in proto-oncogenes caused by reciprocal chromosome translocations have been implicated in the etiology of specific histologic groups. In this study, we examined the contribution of the cell cycle inhibitor genes P15, P16, and P18 to pathogenesis in a large panel of 209 cytogenetically characterized B-cell NHL tumors representing varied histologic groups. We identified the homozygous deletion of P15 and P16 genes in 13 tumors from 12 patients, all belonging to diffuse large-cell histology; 10 had this diagnosis made on presentation, 1 had transformed from small lymphocytic lymphoma, and 1 had transformed from Hodgkin's disease. Tumor-specific point mutations were not identified in the coding regions of these genes. Cytogenetically, chromosome 9p was normal in all but one tumor. On the other hand, eight tumors hemizygous for 9p by cytogenetic analysis showed wild-type configuration of these genes. Our study, therefore, indicates that deletion of P15 and P16 occurs in about 15% of diffuse large-cell NHL and is not usually detected by cytogenetic analysis. P18 was wild-type in all tumors including the 13 tumors hemizygous for 1p.