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  • Oncogenomics
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Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array

Oncogene volume 26, pages 5300–5308 (2007)Cite this article

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.

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Abbreviations

OSCC:

oral squamous cell carcinoma

HD:

homozygous deletion

LOH:

loss of heterozygosity

FISH:

fluorescence in situ hybridization

CGH:

comparative genomic hybridization

BAC:

bacterial artificial chromosome

LCM:

laser-capture microdissection

RT-PCR:

reverse transcriptase-polymerase chain reaction

MSP:

methylation-specific PCR

DMSO:

dimethyl sulfoxide

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Acknowledgements

We thank the patients and their families for helping and participating in this work. We are grateful to Dr Norio Takahashi for performing preliminary experiments and helpful discussion about CGH array. This study was supported in part by grant-in-aids from the Ministry of Education, Culture, Sports, Science and Technology, Japan and from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Organ Function Regenerative and Reconstructive Surgery, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan

    K Nakaya, K-i Nakashiro & H Hamakawa

  2. Department of Preventive Medicine, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan

    H D Yamagata

  3. Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan

    N Arita & M Nose

  4. Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon-city, Ehime, Japan

    T Miki

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  1. K Nakaya
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  2. H D Yamagata
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Correspondence to H D Yamagata.

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Nakaya, K., Yamagata, H., Arita, N. et al. Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array. Oncogene 26, 5300–5308 (2007). https://doi.org/10.1038/sj.onc.1210330

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