Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array.
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.
Nakaya
K
K
Department of Oral and Maxillofacial Surgery, Organ Function Regenerative and Reconstructive Surgery, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan.
Yamagata
H D
HD
Arita
N
N
Nakashiro
K-I
KI
Nose
M
M
Miki
T
T
Hamakawa
H
H
D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D022202:Chromosomes, Artificial, Bacterial; D002894:Chromosomes, Human, Pair 4; D017931:DNA Primers; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006720:Homozygote; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics
D015820:Cadherins; D017931:DNA Primers; C502403:FAT1 protein, human; D012333:RNA, Messenger