Alterations of the p27KIP1 gene in non-Hodgkin's lymphomas and adult T-cell leukemia/lymphoma.
The protein p27KIP1 belongs to a recently identified family of proteins termed cyclin-dependent kinase inhibitors (CDKIs). These proteins play an important role in regulating cell-cycle progression and loss of their function has been implicated in tumorigenesis. Transforming growth factor beta (TGF-beta) may induce cell growth arrest through p27 activation. TGF-beta often loses its ability to arrest growth of transformed cells; this could potentially occur through a defect in p27. To determine the role of p27 in tumorigenesis, we examined its mutational status in 74 non-Hodgkin's lymphomas (NHLs) (52 of B-cell phenotype, 22 of T-cell phenotype), 5 lymphoma cell lines, and 42 adult T-cell leukemias/lymphomas (ATLs) using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and Southern blot analyses. A nonsense mutation (stop codon) that could result in expression of a truncated nonfunctional p27 protein was detected at codon 76 in one case of acute lymphomatous ATL, but not in matched normal tissues. Previously undescribed polymorphisms were also identified at codon 109 in the lymphomas and at codon 55 in the ATLs. Two homozygous deletions of the p27 gene were detected in one case of B-immunoblastic NHL and in one case of acute ATL by Southern blot hybridization. These results indicate that p27 gene alterations are rare events in NHLs and ATLs, but may play an important role in the pathogenesis of some hematologic malignancies.
Morosétti
R
R
Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine 90048, USA.
Kawamata
N
N
Gombart
A F
AF
Miller
C W
CW
Hatta
Y
Y
Hirama
T
T
Said
J W
JW
Tomonaga
M
M
Koeffler
H P
HP
D001483:Base Sequence; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000235:genetics; D018797:Cell Cycle Proteins; D002460:Cell Line; D002461:Cell Line, Transformed; D003062:Codon; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D004791:Enzyme Inhibitors; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27