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

Background and Objectives. The cyclin D1 gene, CCND1, is alternatively spli ced to produce transcripts [a] and [b] in a manner apparently modulated by a polymorphism (A/G) at codon 241, Studies have indicated that the polymorp hism can affect the prognosis of patients with different types of solid tum ors. This study aimed to determine the relative levels of transcripts [a] a nd [b] in normal and malignant peripheral blood mononuclear cells (PBMNC), and to investigate whether these were influenced by the polymorphism. The i mpact of the polymorphism on the survival of a group of mantle cell lymphom a (MCL) patients was also to be studied. Design and Methods. The polymorphism was genotyped, using restriction fragm ent length polymorphism analysis, in 74 patients (42 MCL, 19 chronic lympho cytic leukemia, 13 normal controls) and the relative level of transcripts l a] and [bl determined using a competitive reverse transcription polymerase chain reaction method. Kaplan-Meier survival curves and the log-rank test w ere 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 exp ressed in normal PBMNC and malignant lymphocytes, with the polymorphism aff ecting their relative levels. Neither the predominant transcript, nor genot ype, 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 h omozygous G patients had more transcript [b]. In the small cohort studied, the polymorphism did not appear to affect the prognosis of the patients wit h MCL. (C) 2001, Ferrata Storti Foundation.