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Quantitative analysis of promoter hypermethylation in multiple genes in osteosarcoma
Author(s) -
Hou Peng,
Ji Meiju,
Yang Bin,
Chen Zaozao,
Qiu Junjun,
Shi Xin,
Lu Zuhong
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21762
Subject(s) - osteosarcoma , dna methylation , methylation , epigenetics , cpg site , cancer research , gene , methyltransferase , polymerase chain reaction , promoter , biology , medicine , microbiology and biotechnology , genetics , gene expression
BACKGROUND Osteosarcoma is the most common solid malignant diseases of childhood, occurring in approximately 6 children per million annually; however, to the authors' knowledge to date, the cause of osteosarcoma has remained mostly unknown. Genetic alterations of genes that are specific for osteosarcoma have not been identified. Genetic alternations in the status of DNA methylation, known as epigenetic alterations, are the most common molecular alterations in human neoplasia. Aberrant methylation in the promoter region of tumor‐related genes is associated closely with epigenetically mediated gene silencing, which is a common feature in human tumors. METHODS The authors analyzed CpG islands of 5 different gene loci for aberrant methylation profiles in 30 pairs of osteosarcoma and corresponding normal tissues by using the quantitative methylation‐specific polymerase chain reaction method. The objectives of this study were to characterize the methylation changes in osteosarcoma more extensively and to identify epigenetic biomarkers that may be useful in the diagnosis and prevention of osteosarcoma. RESULTS For the Ras effector homologue ( RASSF1A ), tissue inhibitor of metalloproteinase 3 ( TIMP3 ), O‐6‐methylguanine DNA methyltransferase ( MGMT ), and death‐associated protein kinase 1 ( DAPK1 ) genes, significant differences were observed in the degree of hypermethylation between tumors and normal tissues ( P < 0.01 and P < 0.001, respectively). Measurement of the cumulative multiple promoter hypermethylation revealed striking differences between tumor specimens and normal tissues ( t = 7.31; P < .001). There also was a significant difference in the levels of DNA methylation between the metastatic and nonmetastatic high‐grade osteosarcomas ( t = 4.57; P < .01). In addition, the methylation levels were associated closely with gender ( t = 6.44; P < .001). CONCLUSIONS The results indicated that tumor tissues from patients with osteosarcoma had a significantly higher incidence of hypermethylation for several genes compared with corresponding normal tissues. The epigenetic changes observed in this study may have prognostic importance for patients with osteosarcoma. Cancer 2006. © 2006 American Cancer Society.