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De novo methylation of tumor suppressor gene p16/INK4a is a frequent finding in multiple myeloma patients at diagnosis

Leukemia volume 14, pages 183–187 (2000)Cite this article

Abstract

The p16 gene competes with cyclin D for binding to CDK4/CDK6 and therefore inhibits CDK4/6 complex kinase activity, resulting in dephosphorylation of pRb and related G1 growth arrest. Inactivation of this gene has been involved in a variety of tumors by different mechanisms: homozygous/hemyzygous deletions, point mutations and methylation of a 5′ CpG island into exon E1α of the p16 gene. Homozygous deletions have been rarely found in multiple myeloma (MM) and no point mutations have been reported. Two recent studies have reported a high prevalence of methylation in the exon E1α of the p16 gene, but included only a small number of cases. We have analyzed the methylation pattern of exon E1α of the p16 gene in 101 untreated MM and five primary plasma cell leukemias (PCL). A PCR assay, relying on the inability of some restriction enzymes to digest methylated sequences, was used to analyze the methylation status. Southern blot analysis was used to confirm these results. Forty-one of 101 MM patients (40.5%) as well as four of the five (80%) primary PCL patients had shown methylation of the exon E1α. Our study confirms that hypermethylation of the p16 gene is a frequent event in MM.

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Acknowledgements

We thank F Garcia, B Martínez-Delgado and M Anderson for their technical assistance. This work has been partially supported by FIS/SS 98/1156.

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  1. Service of Hematology, University Hospital of Salamanca, Paseo San Vicente, 58–182, Salamanca, 37007, Spain

    M González, MV Mateos, R García-Sanz, A Balanzategui, R López-Pérez, MC Chillón, D González, I Alaejos & JF San Miguel

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González, M., Mateos, M., García-Sanz, R. et al. De novo methylation of tumor suppressor gene p16/INK4a is a frequent finding in multiple myeloma patients at diagnosis. Leukemia 14, 183–187 (2000). https://doi.org/10.1038/sj.leu.2401617

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