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The cyclin D1 alternative transcripts [a] and [b] are expressed in normal and malignant lymphocytes and their relative levels are influenced by the polymorphism at codon 241
Author(s): Howe D, Lynas C
Source: HAEMATOLOGICA    Volume: 86    Issue: 6    Pages: 563-569    Published: JUN 2001  
Times Cited: 39     References: 17     
Abstract: Background and Objectives. The cyclin D1 gene, CCND1, is alternatively spliced to produce transcripts [a] and [b] in a manner apparently modulated by a polymorphism (A/G) at codon 241, Studies have indicated that the polymorphism can affect the prognosis of patients with different types of solid tumors. This study aimed to determine the relative levels of transcripts [a] and [b] in normal and malignant peripheral blood mononuclear cells (PBMNC), and to investigate whether these were influenced by the polymorphism. The impact of the polymorphism on the survival of a group of mantle cell lymphoma (MCL) patients was also to be studied.

Design and Methods. The polymorphism was genotyped, using restriction fragment length polymorphism analysis, in 74 patients (42 MCL, 19 chronic lymphocytic leukemia, 13 normal controls) and the relative level of transcripts la] and [bl determined using a competitive reverse transcription polymerase chain reaction method. Kaplan-Meier survival curves and the log-rank test were used to analyze the survival data.

Results. Of the cases genotyped, 39 were heterozygous for the polymorphism, 24 homozygous G and 11 homozygous A. Both transcripts [a] and [b] were expressed in normal PBMNC and malignant lymphocytes, with the polymorphism affecting their relative levels. Neither the predominant transcript, nor genotype, significantly influenced survival of the MCL patients studied.

Interpretation and Conclusions. Contrary to previous reports, patients who were homozygous A at the polymorphism produced more transcript [a] whilst homozygous G patients had more transcript [b]. In the small cohort studied, the polymorphism did not appear to affect the prognosis of the patients with MCL. (C) 2001, Ferrata Storti Foundation.

Document Type: Article
Language: English
Reprint Address: Howe, D (reprint author), Taunton & Somerset NHS Trust, Leukaemia Res Unit, Musgrove Pk Hosp, Taunton TA1 5DA, Somerset England
Addresses:
1. Taunton & Somerset NHS Trust, Leukaemia Res Unit, Musgrove Pk Hosp, Taunton TA1 5DA, Somerset England
2. Derriford Hosp, Combined Lab, Plymouth PL6 8DH, Devon England
Publisher: FERRATA STORTI FOUNDATION, STRADA NUOVA 134, 27100 PAVIA, ITALY
Subject Category: Hematology
IDS Number: 446QX
ISSN: 0390-6078
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