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ALTERATIONS OF THE P27(KIP1) GENE IN NON-HODGKINS-LYMPHOMAS AND ADULT T-CELL LEUKEMIA/LYMPHOMA
Author(s): MOROSETTI R, KAWAMATA N, GOMBART AF, MILLER CW, HATTA Y, HIRAMA T, SAID JW, TOMONAGA M, KOEFFLER HP
Source: BLOOD    Volume: 86    Issue: 5    Pages: 1924-1930    Published: SEP 1 1995  
Times Cited: 104     References: 60     
Abstract: 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 deter mine the role of 927 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. (C) 1995 by The American Society of Hematology.
Document Type: Article
Language: English
Reprint Address: MOROSETTI, R (reprint author), UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, SCH MED, DEPT MED, DIV HEMATOL ONCOL, LOS ANGELES, CA 90048 USA
Addresses:
1. UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR, SCH MED, DEPT PATHOL, LOS ANGELES, CA 90048 USA
2. NAGASAKI UNIV, SCH MED, DEPT HEMATOL, NAGASAKI, JAPAN
Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399
Subject Category: Hematology
IDS Number: RT386
ISSN: 0006-4971
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