TY - JOUR
T1 - Discovery of novel epigenetic markers in non-Hodgkin's lymphoma
AU - Shi, Huidong
AU - Guo, Juyuan
AU - Duff, Deiter J.
AU - Rahmatpanah, Farahnaz
AU - Chitima-Matsiga, Rebecca
AU - Al-Kuhlani, Mufadhal
AU - Taylor, Kristen H.
AU - Sjahputera, Ozy
AU - Andreski, Melinda
AU - Wooldridge, James E.
AU - Caldwell, Charles W.
N1 - Funding Information:
We thank Susan Souchek and Kathy Olson for their assistance in cell banking and flow cytometric analysis and Angel Surdin for her expert editorial assistance and contributions to writing this manuscript. This study was supported by National Cancer Institute grants CA100055 and CA097880 (C.W.C.) and grants from the CRC Missouri Chair in Cancer Research, P50 CA097274 (J.E.W.) and the Multiple Myeloma Research Foundation (H.S.).
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgl092
DO - 10.1093/carcin/bgl092
M3 - Article
C2 - 16774933
AN - SCOPUS:33845611987
SN - 0143-3334
VL - 28
SP - 60
EP - 70
JO - Carcinogenesis
JF - Carcinogenesis
IS - 1
ER -