Deletion of cyclin-dependent kinase 4 inhibitor genes P15 and P16 in non-Hodgkin's lymphoma.
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.
Koduru
P R
PR
Department of Laboratories, North Shore University Hospital, Manhasset, NY 11030, USA.
Zariwala
M
M
Soni
M
M
Gong
J Z
JZ
Xiong
Y
Y
Broome
J D
JD
D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000648:ultrastructure; D002893:Chromosomes, Human, Pair 3 / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000648:ultrastructure; D051358:Cyclin-Dependent Kinase 4; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; C493971:CDKN2C protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases