[Molecular genetic progression on nasopharyngeal carcinoma]

The aim of this paper was to discuss the molecular genetic events in the development and progression of nasopharyngeal carcinoma (NPC), and the correlation between genetic alterations and clinicopathological changes of NPC. Analyzed by LOH (loss of heterozygosity) and CGH (comparative genomic hybridization) in primary NPC, high frequent allelic losses were observed on chromosomes 1p, 3p, 9p, 9q, 11q, 13q, 14q, 16q, and 19q, and the minimum deletion regions were also localized; there are closely association between LOH on certain deletion regions in NPC and the clinicopathological parameters. In the group of NPC with higher LOH value (FAL), together with higher antibody titers of EBV IgA/VCA and IgA/EA, most of the NPC showed more invasive of primary T stage (T3 + T4), TNM (III + IV stage) and far lymph node metastasis. High frequent chromosomal gain regions were observed on chromosomes 1q, 2q, 3q, 6p, 6q, 7q11.2, 8q, 11q13, 12, 15q, 17q, and 20q, indicating that there may exist oncogenes which are activated on the gain regions in NPC. CGH analysis showed that gains on chromosome 1q, 8q, 18q, and loss on 9p were closely related to advanced stage of NPC. LOH study also showed high frequent LOH on 3p in normal nasopharyngeal epithelium (74%) and dysplasia lesions (75%) from the Southern Chinese, suggesting that LOH at 3p may be an earlier genetic event of NPC tumorigenesis. Linkage analysis indicate that the HLA gene and cytochrome p4502E gene may be susceptibility genes of NPC. New potential susceptibility gene locus has also been localized by this study. cDNA microarray demonstrated differential expression of cell cycle proteins, anti-apoptotic factors, oncogenes/tumor suppressors, growth-enhancing factors of EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain; differential expression were also observed in different clinical stage NPC. Genetic instabilities (losses and gains) are common molecular events in NPC, and play very important role in the development and progression of NPC. Through LOH, CGH, linkage, and cDNA microarray study, we can find specific biomarkers of NPC, and will support us biomarkers which can be used for earlier diagnosis and prognosis of NPC. More importantly, these biomarkers may be useful in the development of a NPC molecular staging system, which could augment current clinicopathological classification and staging systems.