Frequent methylation of p16INK4A/p14ARF promoters in tumorigenesis of Epstein-Barr virus transformed lymphoblastoid cell lines

Etelka Nagy, G. Veress, K. Szarka, Eszter Csoma, Zoltán Beck

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The data that the p16INK4A gene is frequently inactivated in Burkitt lymphoma (BL) and that this event often accompanies the inactivation of p14ARF in several tumours prompted us to examine the genetic and methylation status of both genes in BL and B-lymphoblastoid cell lines (LCLs). Materials and Methods: The existence of gene deletion, mutation and promoter methylation was investigated by single-strand conformational polymorphism, direct sequencing and methylation-specific PCR (MSP) analysis, respectively. Results: Sequencing of each exon of both tumour suppressor genes revealed p16INK4A mutation only in 3 out of 11 BL, but 1 of them also affected the p14ARF gene. MSP analysis of promoters showed p16 INK4A to be methylated and p14ARF not to be methylated in each Epstein-Barr virus-positive BL cell line. Primary B-cells and de novo established LCLs had no genetic changes or methylated promoter of either gene. LCLs achieving the stage of immortalization usually showed methylation of both p16INK4A and p14ARF promoters. Conclusion: Our results suggest that, in contrast to p16INK4A, inactivation of p14 ARF by either genetic change or promoter methylation has no importance in the development of BL cell lines, while its methylation has a central role in the immortalization of LCLs.

Original languageEnglish
Pages (from-to)2153-2160
Number of pages8
JournalAnticancer Research
Volume25
Issue number3 B
Publication statusPublished - May 2005

Fingerprint

Tumor Suppressor Protein p14ARF
Transformed Cell Line
Human Herpesvirus 4
Methylation
Burkitt Lymphoma
Carcinogenesis
Cell Line
Cyclin-Dependent Kinase Inhibitor p16
Genes
p16 Genes
Polymerase Chain Reaction
Sequence Deletion
Gene Deletion
Tumor Suppressor Genes
Exons
B-Lymphocytes
Mutation

Keywords

  • Burkitt lymphoma
  • Genetic change
  • LCL
  • p14
  • p16
  • Promoter methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Frequent methylation of p16INK4A/p14ARF promoters in tumorigenesis of Epstein-Barr virus transformed lymphoblastoid cell lines. / Nagy, Etelka; Veress, G.; Szarka, K.; Csoma, Eszter; Beck, Zoltán.

In: Anticancer Research, Vol. 25, No. 3 B, 05.2005, p. 2153-2160.

Research output: Contribution to journalArticle

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