Epigenetic analysis of childhood acute lymphoblastic leukemia

Thomas L. Dunwell, Luke B. Hesson, Tatiana Pavlova, Veronika Zabarovska, Vladimir Kashuba, Daniel Catchpoole, Raffaella Chiaramonte, Anna T. Brini, Mike Griffiths, Eamonn R. Maher, Eugene Zabarovsky, Farida Latif

Research output: Contribution to journalArticle

Abstract

We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B", α) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, β) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2′-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalEpigenetics
Volume4
Issue number3
DOIs
Publication statusPublished - Apr 1 2009

Keywords

  • Chromosome 3
  • Epigenetics
  • Gene expression
  • Leukaemia
  • NotI microarray

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Epigenetic analysis of childhood acute lymphoblastic leukemia'. Together they form a unique fingerprint.

  • Cite this

    Dunwell, T. L., Hesson, L. B., Pavlova, T., Zabarovska, V., Kashuba, V., Catchpoole, D., Chiaramonte, R., Brini, A. T., Griffiths, M., Maher, E. R., Zabarovsky, E., & Latif, F. (2009). Epigenetic analysis of childhood acute lymphoblastic leukemia. Epigenetics, 4(3), 185-193. https://doi.org/10.4161/epi.4.3.8752