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Clinical Cancer Research Vol. 6, 357-362, February 2000
© 2000 American Association for Cancer Research

Advances in Brief

Use of Allelic Loss to Predict Malignant Risk for Low-grade Oral Epithelial Dysplasia1

Miriam P. Rosin, Xing Cheng, Catherine Poh, Wan L. Lam, Yongqian Huang, John Lovas, Ken Berean, Joel B. Epstein, Robert Priddy, Nhu D. Le and Lewei Zhang2

British Columbia Cancer Agency/Cancer Research Centre, Vancouver, British Columbia, V5Z 4E6 Canada [M. P. R., W. L. L., J. B. E., N. D. L.]; School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, V5A 1S6 Canada [M. P. R., X. C., Y. H.]; Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada [X. C., C. P., J. B. E., R. P., L. Z.]; Faculty of Dentistry, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 Canada [J. L.]; Vancouver General Hospital, Vancouver, British Columbia, V5Z 1M9 Canada [K. B., J. B. E.]; and School of Dentistry, University of Washington, Seattle, Washington 98195 [J. B. E.]

One of the best approaches to identifying genetic changes critical to oral cancer progression is to compare progressing and nonprogressing oral premalignant lesions. However, such samples are rare, and they require long-term follow-up. The current study used the large archive network and clinical database in British Columbia to study loss of heterozygosity (LOH) in cases of early oral premalignancies, comparing those with a history of progression to carcinoma in situ or invasive cancer and those without a history of progression (referred to as nonprogressing cases). Each of 116 cases was analyzed for LOH at 19 microsatellite loci on seven chromosome arms (3p, 4q, 8p, 9p, 11q, 13q, and 17p). The progressing and nonprogressing cases showed dramatically different LOH patterns of multiple allelic losses. An essential step for progression seems to involve LOH at 3p and/or 9p because virtually all progressing cases showed such loss. However, LOH at 3p and/or 9p also occurred in nonprogressing cases. Individuals with LOH at 3p and/or 9p but at no other arms exhibit only a slight increase of 3.8-fold in relative risk for developing cancer. In contrast, individuals with additional losses (on 4q, 8p, 11q, or 17p), which appeared uncommon in nonprogressing cases, showed 33-fold increases in relative cancer risk. In conclusion, analysis of LOH at 3p and 9p could serve as an initial screening for cancer risk of early premalignancies. Follow-up investigation for additional losses would be essential for predicting cancer progression.




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