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Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array
- Source :
- Oncogene. 26(36)
- Publication Year :
- 2007
-
Abstract
- Homozygous deletions (HD) provide an important resource for identifying the location of candidate tumor suppressor genes. To identify the tumor suppressor gene in oral cancer, we employed high-resolution comparative genomic hybridization (CGH)-array analysis. We identified a homozygous loss of FAT (4q35), a new member of the human cadherin superfamily, from genome-wide screening of copy number alterations in one primary oral cancer. This result was evaluated by genomic polymerase chain reaction in 13 oral cancer cell lines and 20 primary oral cancers and Southern blot in the cell lines. We found frequent exonic HD of FAT in the cell lines (3/13, 23%) and in primary oral cancers (16/20, 80%). FAT expression was absent in these cell lines. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). Moreover, loss of gene expression was identified in other types of squamous cell carcinoma. The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Our results identify mutations in FAT as an important factor in the development of oral cancer and indicate the importance of FATs function in some squamous cell carcinomas.
- Subjects :
- Cancer Research
Chromosomes, Artificial, Bacterial
Tumor suppressor gene
Biology
medicine.disease_cause
Exon
Cell Line, Tumor
Gene expression
Genetics
medicine
Humans
Genes, Tumor Suppressor
RNA, Messenger
Molecular Biology
DNA Primers
Base Sequence
Cadherin
Homozygote
Cancer
Nucleic Acid Hybridization
medicine.disease
Cadherins
Molecular biology
stomatognathic diseases
CpG site
Carcinoma, Squamous Cell
Mouth Neoplasms
Chromosomes, Human, Pair 4
Carcinogenesis
Gene Deletion
Comparative genomic hybridization
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 26
- Issue :
- 36
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....564252d9cf2d28ca0e57f9dfa9771343