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Quantitative evaluation of p16INK4a promoter methylation using pyrosequencing in de novo diffuse large B-cell lymphoma

Zainuddin, Norafiza and Kanduri, Meena and Berglund, Mattias and Lindell, Monica and Amini, Rose-Marie and Roos, Göran and Sundström, Christer and Enblad , Gunilla and Rosenquist, Richard (2011) Quantitative evaluation of p16INK4a promoter methylation using pyrosequencing in de novo diffuse large B-cell lymphoma. Leukemia Research, 35 (4). pp. 438-443. ISSN 0145-2126

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Abstract

The p16INK4a tumor suppressor gene can be inactivated by a variety of events including promoter hypermethylation. In diffuse large B-cell lymphoma (DLBCL), p16INK4a methylation has been associated with advanced disease stage and higher IPI. The prognostic impact of p16INK4a methylation in DLBCL remains unclear; however, it has been suggested to correlate with inferior outcome. To further investigate the clinical impact of p16INK4a methylation in DLBCL, promoter methylation of this gene was assessed quantitatively by pyrosequencing. Forty-two of 113 (37%) DLBCL patients with methylation level above 5% were categorized as methylated and subsequently divided into low, intermediate and high methylation categories. Overall, no association was shown between the extent of p16INK4a methylation and patients’ clinical characteristics, except disease stage (P = 0.049). Moreover, we could not reveal any impact of p16INK4a methylation on lymphoma-specific survival. Although >25% of p16INK4a methylation correlated with a better progression-free survival (P = 0.048) in patients <65 years old, the significance of this finding, if any, needs to be further investigated. In conclusion, our finding questions the role of p16INK4a promoter methylation as a negative prognostic factor in DLBCL.

Item Type: Article (Journal)
Additional Information: 4623/4588
Uncontrolled Keywords: Diffuse large B-cell lymphoma, p16INK4a, Hypermethylation, Pyrosequencing, Methylation-specific PCR
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Allied Health Sciences > Department of Basic Health Sciences (Until June 2011)
Depositing User: Dr. Norafiza Zainuddin
Date Deposited: 26 Sep 2011 10:31
Last Modified: 20 Jun 2013 11:00
URI: http://irep.iium.edu.my/id/eprint/4588

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