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.
OBJECTIVE
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.


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 [a] and [b] 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.


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.
Howe
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Leukaemia Research Unit, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, TA1 5DA, UK. denise.howe@tauntonsom-tr.swest.nhs.uk
Lynas
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D012333:RNA, Messenger; D019938:Cyclin D1