Saranath D, Bhoite L T, Deo M G
Cell and Developmental Pathology Division, Cancer Research Institute, Bombay, India.
Eur J Cancer B Oral Oncol. 1993 Apr;29B(2):107-12. doi: 10.1016/0964-1955(93)90031-9.
Carcinogenesis is a multi-step process including aberrant expression of two interacting classes of genes--oncogenes and tumour suppressor genes. With recent technological advances, it is feasible to identify the various molecular lesions underlying the different stages of neoplasia. Squamous cell carcinomas of the head and neck, although representing 2-4% of the malignancies in the West, comprise a large fraction (40%) of total cancers in India, posing a major health problem. Further, epidemiological and experimental evidence unequivocally confirms a causal association between tobacco chewing habit, highly prevalent in India, and oral cancers. Thus, the oral cancers offer an excellent in vivo system for the study of the environmental tobacco-carcinogen induced molecular alterations in the malignancy, and associated premalignant lesions such as leukoplakia. With a view to elucidating the molecular lesions involving oncogenes in oral carcinogenesis, we have investigated myc/ras/EGF-R activation by amplification, point mutation, gene rearrangement and allelic losses. Further, a functionally activated potent transforming gene was detected in a NIH3T3 transfection/tumorigenicity assay, unrelated to myc/ras/EGF-R. Studies on the involvement of p53 gene in oral cancer, indicates p53 allelic loss as an event observed in leukoplakia and tumour tissues. Advanced oral cancer stages demonstrate cumulative molecular aberrations, with greater than 95% samples showing oncogene involvement, thus indicating a multi-step process of oral carcinogenesis. The review presents a comparative picture of the oral malignancies seen in Western countries and India, significance of molecular lesions and future perspectives of oncogenes and tumour suppressor gene involvement in oral cancer.
癌症发生是一个多步骤过程，包括两类相互作用基因——癌基因和肿瘤抑制基因的异常表达。随着最近技术的进步，确定肿瘤形成不同阶段潜在的各种分子损伤是可行的。头颈部鳞状细胞癌在西方占恶性肿瘤的2 - 4%，但在印度却占全部癌症的很大一部分（40%），构成了一个重大的健康问题。此外，流行病学和实验证据明确证实了在印度高度流行的嚼烟习惯与口腔癌之间存在因果关联。因此，口腔癌为研究环境烟草致癌物诱导的恶性肿瘤以及相关癌前病变（如白斑）中的分子改变提供了一个极佳的体内系统。为了阐明口腔癌发生过程中涉及癌基因的分子损伤，我们通过扩增、点突变、基因重排和等位基因缺失研究了myc/ras/表皮生长因子受体（EGF-R）的激活情况。此外，在NIH3T3转染/致瘤性试验中检测到一个功能激活的强效转化基因，它与myc/ras/EGF-R无关。关于p53基因在口腔癌中的作用研究表明，p53等位基因缺失是在白斑和肿瘤组织中观察到的一个现象。晚期口腔癌阶段显示出累积的分子异常，超过95%的样本显示有癌基因参与，从而表明口腔癌发生是一个多步骤过程。这篇综述呈现了西方国家和印度口腔恶性肿瘤的对比情况、分子损伤的重要性以及癌基因和肿瘤抑制基因在口腔癌中的作用的未来展望。
