Journal Article

Characterization of the murine p19<sup><i>ARF</i></sup> promoter CpG island and its methylation pattern in primary lymphomas

Bárbara Meléndez, Marcos Malumbres, Ignacio Pérez de Castro, Javier Santos, Angel Pellicer and José Fernández-Piqueras

in Carcinogenesis

Volume 21, issue 4, pages 817-821
Published in print April 2000 | ISSN: 0143-3334
Published online April 2000 | e-ISSN: 1460-2180 | DOI:
Characterization of the murine p19ARF promoter CpG island and its methylation pattern in primary lymphomas

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The INK4a/ARF locus encodes two different proteins involved in cell cycle control. Both molecules, p16INK4a and p19ARF, inhibit cell cycle progression and have been shown to act as tumor suppressors in a variety of models. Their expression is controlled by separate promoters responding to different stimuli and they therefore show independent transcriptional regulation. We have cloned and characterized a 2.5 kb region upstream of the murine p19ARF gene to determine the role of DNA methylation in suppressing p19ARF transcription in a wide panel of murine primary T cell lymphomas. This region contains a DNA fragment with the characteristics of a CpG island similar to those described for the murine p16INK4a and p15INK4b genes. Expression of p19ARF is decreased in a significant number (20%) of the murine lymphomas analyzed. Overexpression of the p19ARF transcript is also frequent, suggesting alterations in molecules of the retinoblastoma or p53 pathways that are involved in p19ARF regulation. Although hypermethylation of the INK4a and INK4b promoters is frequently involved in murine lymphomas, the p19ARF CpG island is infrequently methylated in the murine primary lymphomas studied in this work. Since loss of p19ARF expression cannot be explained as the result of homozygous deletions or hypermethylation of the ARF gene, other regulatory mechanisms seem to be altered in these malignancies.

Keywords: Rb, retinoblastoma; pRb, retinoblastoma protein.

Journal Article.  4071 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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