Summary
The Harveyras locus was examined for restriction fragment polymorphism and loss of allelic heterozygosity in 62 oral cancer patients. Southern blot analysis onBamHI digests of the tumour tissue DNA, revealed 23 patients with H-ras-1 heterozygosity. The probes used to study the polymorphism were theBamHI 6.6-kb fragment encoding the complete H-ras-1 sequence plus the variable tandem repeat (VTR) region, and the 1-kbMspI fragment encoding the VTR region. The allelic heterozygosity was better resolved byPvuII and further confirmed byTaqI. In addition,TaqI digestion demonstrated a unique VTR rearrangement indicated by 2.1-kb, 0.9-kb and 0.6-kb fragments, implying additionalTaqI sites, in three of the patients. Further analysis of matched tumor tissue and peripheral blood cell DNA from the same patient demonstrated tumor-associated loss of one of the allelic fragments in 7/23 (30%) of the patients with H-ras-1 heterozygosity. However, the loss was not significantly correlated to clinicopathological parameters staging the disease. Thus, our data showing loss of H-ras-1 alleles and VTR rearrangement, with relatively high incidence (9/23; 39%) in the oral cancer patients at various stages of the disease, implies H-ras-1 involvement as an early event in the process of oral carcinogenesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- VTR:
-
variable tandem repeat
- PBC:
-
peripheral blood cell
- RFLP:
-
restriction fragment length polymorphism
- EGFR:
-
epidermal growth factor receptor
References
Ali IU, Liderau R, Theillet C, Callahan R (1987) Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia. Science 238:185–188
Binnie WH (1976) Epidemiology and etiology of oral cancer in Britain. Proc R Soc Med 69:737–740
Binnie WH (1991) Risk factors and risk markers for oral cancers in low risk areas of the world. In: Johnson NW (ed) Oral cancers: the detection of patients and lesions at risk, vol 2. Cambridge University Press, UK (in press)
Capon D, Chen E, Levinson A, Seeburg P, Goeddel D (1983) Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature 302:33–37
Daftary D (1991) Risk factors and risk markers for oral cancers in high risk areas of the world. In: Johnson NW (ed) Oral cancer: the detection of patients and lesions at risk, vol 2. Cambridge University Press, UK (in press)
Fearon E, Feinberg A, Hamilton S, Vogelstein B (1985) Loss of genes on the short arm of chromosome 11 in bladder cancer. Science 318:377–380
Field J, Spandidos D (1987) Expression of oncogenes in human tumors with special reference to the head and neck region. J Oral Pathol 16:97–107
Gupta PC, Mehta FS, Pindborg JJ, Aghi MB, Bhonsle RB, Murti PR (1987) An educational intervention study for tobacco chewing and smoking habits among Indian villagers. In: Aoki M, Hisamichi S, Tominaga S (eds) Smoking and health. Excerpta Medica, Amsterdam, pp 623–626
Heighway J, Thatcher N, Cerny T, Hasleton P (1986) Genetic predisposition to human lung cancer. Br J Cancer 53:453–457
Jussawala D, Deshpande V (1971) Evaluation of cancer risk in tobacco chewers and smokers: an epidemiologic assessment. Cancer 28:244–252
Klein G (1987) Approaching era of the tumor suppressor genes. Science 238:1539–1545
Krontiris T, Dimartino N, Colb M, Parkinson D (1985) Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumor DNAs of cancer patients. Nature 313:369–374
Lee J, Kavanagh J, Wharton J, Widrick D, Blick M (1989) Allele loss at the c-Ha-ras-1 locus in human ovarian cancer. Cancer Res 49:1220–1222
Pierotti M, Radice P, Biunno I, Borrello M, Cattadori M, Porta G (1986) Detection of two TaqI polymorphisms in the VTR region of the human H-ras-1 oncogene. Cytogenet Cell Genet 43:174–180
Reeve A, Shih S, Raizis A, Feinberg A (1989) Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells. Mol Cell Biol 9:1799–1803
Sambrook J, Fritsch E, Maniatis T (1989a) Molecular Cloning: a laboratory manual, vol 2. Cold Spring Harbor Laboratory, New York, pp 9.16–9.19
Sambrook J, Fritsch E, Maniatis T (1989b) Moleclar cloning: a laboratory manual, vol 1. Cold Spring Harbor Laboratory, New York, pp 1.33–1.37
Sanghavi L (1981) Epidemiologic and intervention studies. Screening: cancer epidemiology: the Indian scene. J Cancer Res Clin Oncol 9:1–14
Saranath D, Panchal R, Nair R, Mehta A, Sanghavi V, Sumegi J, Klein G, Deo M (1989) Oncogene amplification in squamous cell carcinoma of the oral cavity. Jpn J Cancer Res 80:430–437
Saranath D, Panchal R, Nair R, Mehta A, Sanghavi V, Deo M (1990) Restriction fragment polymorphism of thel-myc gene in oral cancer patients. Br J Cancer 61:530–533
Saranath D, Chang E, Bhoite L, Panchal R, Kerr I, Mehta A, Johnson N, Deo M (1991) High frequency mutations in codons 12 and 61 of H-ras oncogene in tobacco related human oral carcinomas. Br J Cancer 63:573–578
Shih C, Weinberg R (1982) Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell 29:161–169
Southern E (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 898:503–517
Spandidos DA, Holmes L (1987) Transcriptional enhancer activity in the variable tandem repeat DNA sequence downstream of the human Ha-ras-1 gene. FEBS Lett 218:41–46
Theillet C, Liderau R, Escot C, Hutzell P, Brunet M, Gest J, Schlom J, Callahan R (1986) Cancer Res 46:4776–4781
Union Internationale Contre le Cancer (UICC) (1988) TNM classification of malignant tumors Harmer MN (ed) Geneva
Winn DM (1984) Tobacco chewing and snuff dipping: an association with human cancer. In: O'Neill IK, Borster RC, Miller CT (eds)N-Nitroso compounds: occurrence, biological effects and relevance to human cancer. IARC Scientific Publ no. 57. IARC, Geneva, pp 837–849
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Saranath, D., Bhoite, L.T., Mehta, A.R. et al. Loss of allelic heterozygosity at the harveyras locus in human oral carcinomas. J Cancer Res Clin Oncol 117, 484–488 (1991). https://doi.org/10.1007/BF01612771
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01612771