Extensive analysis of the retinoblastoma gene in adult T cell leukemia/lymphoma (ATL).
The retinoblastoma susceptibility gene (Rb) plays a key role in regulating the cell cycle in association with cyclins and cyclin-dependent kinases (CDKs). Alteration of the Rb gene as well as CDK inhibitors (CDKIs) leads to deregulated cellular growth which promotes cancer formation. We examined the genomic configuration of the entire Rb gene in 40 primary adult T cell leukemias/lymphomas (ATL) and two ATL cell lines by Southern blotting and also by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Homozygous loss of exon 1 was identified in one of 21 acute ATL, one of 15 chronic ATL, and none of four lymphomatous ATL samples. No point mutations were identified. Previously, we found that 10 of these same ATL samples had alterations of either p16(INK4A) (homozygous deletion) or p27(kip1) (homozygous deletion or point mutation). Although the numbers are very low, none of the samples with an aberrant Rb gene had an altered CDKI and vice versa, suggesting that both genes probably operate in a common pathway and alteration of either can provide these cells with a growth advantage.
Hatta
Y
Y
Department of Medicine, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Yamada
Y
Y
Tomonaga
M
M
Koeffler
H P
HP
D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins