Abstract
Recent cytogenetic and molecular studies with highly polymorphic microsatellite markers have implicated allele loss involving chromosome 4 in several human cancers, which suggests the presence of multiple tumor suppressor gene (TSG) loci. However, there has been no detailed analysis of loss of heterozygosity (LOH) on chromosome 4 in oral squamous cell carcinoma (OSCC). To determine the location of a putative TSG associated with OSCC on chromosome 4, polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to 17 loci was performed to screen 32 patients with OSCC. LOH was observed in the majority of the tumors (75%) in at least one of the loci. The loci on the long arm exhibited a significantly higher frequency of deletions (66%) than those of the short arm (25%). Among the loci tested, frequent LOH was centered at D4S1573 on 4q25, which represents a region of about 4 centimorgans (cM). However, no commonly deleted regions were found on the short arm of the chromosome. We detected microsatellite instability (MI) in 31% of the cases. MI was also observed more frequently on the long arm (28%) than the short arm (6%). Thus, our data indicate that alterations of chromosome 4 regions, especially the long arm, are associated with OSCC tumorigenesis and that the 4q25 region may harbor at least one putative TSG.
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References
Ah-See KW, Cooke TG, Pickford IR, Soutar D and Balmain A. . 1994 Cancer Res. 54: 1617–1621.
Chou YH, Chung KC, Jeng LB, Chen TC and Liaw YF. . 1998 Cancer Lett. 123: 1–6.
El-Naggar AK, Hurr K, Batsakis JG, Luna MA, Goepfert H and Huff V. . 1995 Cancer Res. 55: 2656–2659.
Elder PA, Bell SM and Knowles MA. . 1994 Oncogene 9: 3433–3436.
Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millaseau P, Marc S, Bernardi G, Lathrop M and Weissenbach J. . 1994 Nature (Genet.) 7: 246–339.
Hampton GM, Larson AA, Baergen RN, Sommers RL, Kern S and Cavenee WK. . 1996 Proc. Natl. Acad. Sci. USA 13: 6704–6709.
Hammoud ZT, Kaleem Z, Cooper JD, Sundaresan RS, Patterson GA and Goodfellow PJ. . 1996 Cancer Res. 56: 4499–4502.
Larson AA, Kern S, Sommers RL, Yokota J, Cavenee WK and Hampton GM. . 1996 Cancer Res. 56: 1426–-1431.
Leon M and Kew MC. . 1996 Anticancer Res. 16: 349–351.
Marshall CJ. . 1991 Cell 64: 313–326.
Mitra AB, Murty VV, Li RG, Pratap M, Luthra UK and Chaganti RS. . 1994 Cancer Res. 54: 4481–4487.
Nawroz H, van der Riet P, Hruban RH, Kock W, Ruppert JM and Sidransky D. . 1994 Cancer Res. 54: 1152–1155.
Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM and Huebner K. . 1996 Cell 84: 587–597.
Parkin DM, Pisani P and Ferlay J. . 1993 Int. J. Cancer 54: 594–606.
Polascik TJ, Cairns P, Chang WY, Schoenberg MP and Sidransky D. . 1995 Cancer Res. 55: 5396–5399.
Pershouse MA, El-Naggar AK, Hurr K, Lin H, Yung WKA and Steck PA. . 1997 Oncogene 14: 369–373.
Shridhar V, Sun QC, Miller OJ, Kalemkerian GP, Petros J and Smith DI. . 1997 Oncogene 15: 2727–2733.
Uzawa K, Suzuki H, Komiya A, Nakanishi H, Ogawara K, Tanzawa H and Sato K. . 1996 Int. J. Cancer 67: 510–514.
Van Dyke DL, Worshan MJ, Benninger MS, Krause CJ, Baker SR, Wolf GT, Drumheller T, Tilley BC and Carey TE. . 1994 Genes Chromosome Cancer 9: 192–206.
Weinberg RA. . 1991 Science 254: 1138–1146.
Wang XL, Uzawa K, Nakanishi H, Tanzawa H and Sato K. . 1997 Int. J. Oncol. 10: 535–538.
Wang XL, Uzawa K, Miyakawa A, Shiiba M, Watanabe T, Sato T, Miya T, Yokoe H and Tanzawa H. . 1998 Int. J. Cancer 75: 671–674.
Acknowledgements
We thank Jordan A Shavit for critically reading this manuscript. This study was supported by Research Grants from the Ministry of Education, Science and Culture, Japan.
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Wang, XL., Uzawa, K., Imai, F. et al. Localization of a novel tumor suppressor gene associated with human oral cancer on chromosome 4q25. Oncogene 18, 823–825 (1999). https://doi.org/10.1038/sj.onc.1202318
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DOI: https://doi.org/10.1038/sj.onc.1202318
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