Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers
- 4 April 2002
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 21 (15), 2328-2333
- https://doi.org/10.1038/sj.onc.1205402
Abstract
The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.Keywords
This publication has 16 references indexed in Scilit:
- Epigenetic Inactivation of RASSF1A in Lung and Breast Cancers and Malignant Phenotype SuppressionJNCI Journal of the National Cancer Institute, 2001
- Somatic mutation of thehBUB1 mitotic checkpoint gene in primary lung cancerGenes, Chromosomes and Cancer, 2000
- Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3Nature Genetics, 2000
- High frequency of hypermethylation at the 14-3-3 σ locus leads to gene silencing in breast cancerProceedings of the National Academy of Sciences of the United States of America, 2000
- DNA hypermethylation in tumorigenesis: epigenetics joins geneticsTrends in Genetics, 2000
- Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancersOncogene, 1999
- p53, the Cellular Gatekeeper for Growth and DivisionCell, 1997
- Cell Cycle Checkpoints: Preventing an Identity CrisisScience, 1996
- 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancersNature Medicine, 1995
- Abnormalities in Structure and Expression of the Human Retinoblastoma Gene in SCLCScience, 1988