Alterations of methylation in DNA from human lung cancer tissues.
Keshava-N; Huffman-D; Wu-ZL; Ong-T
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California. Philadelphia, PA: American Association for Cancer Research, 2002 Apr; 43:1123
Aberrant methylation pattern is an acquired epigenetic alteration causing inappropriate activation or silencing of a gene. Alterations in DNA methylation have been associated with cancers at almost all tumor sites and represent one of the most consistent changes in neoplastic cells. To determine if global methylation may contribute to the development of lung cancer, we studied genome-wide aberrant methylation pattern in 57 lung cancer cases and matched controls. Methylation was carried out using methylation sensitive restriction DNA fingerprinting analysis. We found that 86% of all the lung cancer tissues were hypermethylated at various sites using short random primers. Many fragments appeared to be differentially methylated. Upon sub-cloning, sequencing and matching several common differentially methylated fragments using the available database (BLAST), we have identified the fragments to encode for human cyclin C (CGNG), Wilms tumor (WT-1), Nuclear factor-kB (NF-kB) genes. Analysis of fragments among tumor types revealed that 49% of the hypermethylated fragments were adenocarcinomas, 30% were squamous cell carcinomas and 21 % belonged to other types. When age or sex was considered as a factor, no significant difference in any of these groups was observed. Methylation pattern was unrelated to smoking status of the patients. We also studied the methylation status of the tumor suppressor p16 gene using bisulfide modification method. Hypermethylation in the p16 gene was observed in 45/60 samples (75%). Our overall results indicate that hypermethylation seems to play an important role in the development of lung cancer. Further studies are in progress to elucidate the molecular mechanism(s) of hypermethylation in lung cancer.
DNA-damage; Genetics; Genes; Gene-mutation; Cancer; Lung-cancer; Lung-disorders; Respiratory-system-disorders; Age-factors; Sex-factors; Smoking
Abstract; Conference/Symposia Proceedings
Research Tools and Approaches: Cancer Research Methods
Proceedings of the 93rd American Association for Cancer Research Annual Meeting, April 6-10, 2002, San Francisco, California