The first 2 authors contributed equally to this work.
Multiple gene methylation of nonsmall cell lung cancers evaluated with 3-dimensional microarray
Article first published online: 19 FEB 2008
Copyright © 2008 American Cancer Society
Volume 112, Issue 6, pages 1325–1336, 15 March 2008
How to Cite
Wang, Y., Zhang, D., Zheng, W., Luo, J., Bai, Y. and Lu, Z. (2008), Multiple gene methylation of nonsmall cell lung cancers evaluated with 3-dimensional microarray. Cancer, 112: 1325–1336. doi: 10.1002/cncr.23312
- Issue published online: 3 MAR 2008
- Article first published online: 19 FEB 2008
- Manuscript Accepted: 19 SEP 2007
- Manuscript Revised: 21 AUG 2007
- Manuscript Received: 28 JAN 2007
- National Natural Science Foundation of China. Grant Number: Project 60121101
- Hi-Tech Research and Development Program of China. Grant Number: Project 2006AA020702
- National Basic Research and Development Program (973 Program) of China. Grant Number: 2006CB705602-9
- polyacrylamide gel;
- DNA microarray;
- linker-polymerase chain reaction;
- DNA methylation
Aberrant DNA methylation of the CpG islands for cancer-related genes is among the earliest and most frequent alterations in cancer and may be useful for diagnosing cancer or evaluating recurrent disease.
In this study, a 3-dimensional (3-D), polyacrylamide gel-based DNA microarray coupled with linker-polymerase chain reaction (PCR) was developed to detect hypermethylation of CpG islands in multiple genes from a large group of different samples. The authors determined the frequency of aberrant promoter methylation of 15 genes in 28 resected primary nonsmall cell lung cancers (NSCLCs) and in 12 corresponding nonmalignant lung tissues.
Methylation frequencies in the tumor samples were detected in 18% of samples for the breast cancer 1 gene BRCA1, in 43% of samples for the tissue inhibitor of metalloproteinase 3 gene TIMP-3, in 38% of samples for the cyclin-dependent kinase inhibitor 4A gene p16INK4a, in 54% of samples for the cadherin 13 gene CDH13, in 50% of samples for the death-associated protein kinase gene DAPK, in 11% of samples for the E-cadherin gene ECAD, in 25% of samples for the insulin-like growth factor binding protein 7 gene IGFBP7, in 18% of samples for the Ras association domain family 1 gene RASSF1, in 68% of samples for the adenomatous polyposis coli gene APC, in 7% of samples for the cyclin-dependent kinase inhibitor gene p15, in 18% of samples for the CD44 cell adhesion molecule gene, in 29% of samples for the human Mut-L homolog gene hMLH, in 32% of samples for the human telomerase reverse transcriptase gene hTERT, in 64% of samples for the calcitonin gene-related polypeptide α gene CALCA, and in 54% of samples for the estrogen receptor gene ER; however, methylation was not observed in the majority of corresponding nonmalignant tissues. Six samples in from 28 tumors had >6 genes methylated, and 1 sample had 13 genes methylated. Methylation of these genes was correlated with some clinicopathologic patient characteristics.
This study demonstrated that a 3-D microarray could be used to detect DNA hypermethylation and provided a high-throughput platform for DNA hypermethylation analysis. Cancer 2008. © 2008 American Cancer Society.