Discovery of novel epigenetic markers in non-Hodgkin's lymphoma

Huidong Shi, Juyuan Guo, Deiter J. Duff, Farahnaz Rahmatpanah, Rebecca Chitima-Matsiga, Mufadhal Al-Kuhlani, Kristen H. Taylor, Ozy Sjahputera, Melinda Andreski, James E. Wooldridge, Charles W. Caldwell

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Abstract

Non-Hodgkin's lymphoma (NHL) is a group of malignancies with heterogeneous genetic and epigenetic alterations. Discovery of molecular markers that better define NHL should improve diagnosis, prognosis and understanding of the biology. We developed a CpG island DNA microarray for discovery of aberrant methylation targets in cancer, and now apply this method to examine NHL cell lines and primary tumors. This methylation profiling revealed differential patterns in six cell lines originating from different subtypes of NHL. We identified 30 hypermethylated genes in these cell lines and independently confirmed 10 of them. Methylation of 6 of these genes was then further examined in 75 primary NHL specimens composed of four subtypes representing different stages of maturation. Each gene (DLC-1, PCDHGB7, CYP27B1, EFNA5, CCND1 and RARβ2) was frequently hypermethylated in these NHLs (87, 78, 61, 53, 40 and 38%, respectively), but not in benign follicular hyperplasia. Although some genes such as DLC-1 and PCDHGB7 were methylated in the vast majority of NHLs, others were differentially methylated in specific subtypes. The methylation of the candidate tumor suppressor gene DLC-1 was detected in a high proportion of primary tumor and plasma DNA samples by using quantitative methylation-specific PCR analysis. This promoter hypermethylation inversely correlated with DLC-1 gene expression in primary NHL samples. Thus, this CpG island microarray is a powerful discovery tool to identify novel methylated genes for further studies of their relevant molecular pathways in NHLs and identification of potential epigenetic biomarkers of disease.

Original languageEnglish (US)
Pages (from-to)60-70
Number of pages11
JournalCarcinogenesis
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2007

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Epigenomics
Non-Hodgkin's Lymphoma
Methylation
CpG Islands
Genes
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Cell Line
Neoplasms
Oligonucleotide Array Sequence Analysis
Tumor Cell Line
Tumor Suppressor Genes
Hyperplasia
Biomarkers
Gene Expression
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Cancer Research

Cite this

Shi, H., Guo, J., Duff, D. J., Rahmatpanah, F., Chitima-Matsiga, R., Al-Kuhlani, M., ... Caldwell, C. W. (2007). Discovery of novel epigenetic markers in non-Hodgkin's lymphoma. Carcinogenesis, 28(1), 60-70. https://doi.org/10.1093/carcin/bgl092

Discovery of novel epigenetic markers in non-Hodgkin's lymphoma. / Shi, Huidong; Guo, Juyuan; Duff, Deiter J.; Rahmatpanah, Farahnaz; Chitima-Matsiga, Rebecca; Al-Kuhlani, Mufadhal; Taylor, Kristen H.; Sjahputera, Ozy; Andreski, Melinda; Wooldridge, James E.; Caldwell, Charles W.

In: Carcinogenesis, Vol. 28, No. 1, 01.01.2007, p. 60-70.

Research output: Contribution to journalArticle

Shi, H, Guo, J, Duff, DJ, Rahmatpanah, F, Chitima-Matsiga, R, Al-Kuhlani, M, Taylor, KH, Sjahputera, O, Andreski, M, Wooldridge, JE & Caldwell, CW 2007, 'Discovery of novel epigenetic markers in non-Hodgkin's lymphoma', Carcinogenesis, vol. 28, no. 1, pp. 60-70. https://doi.org/10.1093/carcin/bgl092
Shi H, Guo J, Duff DJ, Rahmatpanah F, Chitima-Matsiga R, Al-Kuhlani M et al. Discovery of novel epigenetic markers in non-Hodgkin's lymphoma. Carcinogenesis. 2007 Jan 1;28(1):60-70. https://doi.org/10.1093/carcin/bgl092
Shi, Huidong ; Guo, Juyuan ; Duff, Deiter J. ; Rahmatpanah, Farahnaz ; Chitima-Matsiga, Rebecca ; Al-Kuhlani, Mufadhal ; Taylor, Kristen H. ; Sjahputera, Ozy ; Andreski, Melinda ; Wooldridge, James E. ; Caldwell, Charles W. / Discovery of novel epigenetic markers in non-Hodgkin's lymphoma. In: Carcinogenesis. 2007 ; Vol. 28, No. 1. pp. 60-70.
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