Loss of heterozygosity on chromosome 14 in primary nasopharyngeal carcinoma

Multiple genetic alterations are believed to be involved in the pathogenesis of nasopharyngeal carcinomas (NPC). Loss of heterozygosity (LOH) of chromosomes 3p, 9p and 11q were previously reported in NPC. In order to further define the genetic alterations in NPC, 42 pairs of normal and tumor DNA of NPC were examined for LOH on chromosomes 5p, 5q, 6q, 14q, 15q, 16p, 16q, 17q using 16 polymorphic microsatellite markers. Frequent LOH (33%; 7 out of 21 cases) was observed in chromosome 14q at locus D14s81 (14q31). In order to define the common region of deletion, nine polymorphic microsatellite markers on 14q were examined for LOH in NPC. A common region of deletion was defined in NPC at chromosome 14q24.3-q32.1 flanked by two microsatellite markers D14s76 and D14s45. The common region of deletion (14q24.3-32.1) identified in NPC overlapped with the deleted regions of 14q reported in several human cancers. In 2 cases of NPC, the pattern of LOH revealed the presence of another commonly deleted region defined by loci D14s63 and D14s69 (mapped to 14q11.1-24.1) and located proximal to locus D14s76 (14q24.3). This study suggests that multiple tumor suppressor genes present on chromosome 14q are involved in the pathogenesis of NPC.link_to_subscribed_fulltex

Inhibiting tumorigenic potential by restoration of p16 in nasopharyngeal carcinoma

The p16 gene, encodes a key checkpoint protein p16 in the cell cycle, has been reported inactivation in a wide variety of human cancers. We have previously demonstrated high frequency of p16 alterations in primary nasopharyngeal carcinoma (NPC), xenografts and cell lines. The finding implied that inactivation of the p16 gene may play an important role in the NPC development. To investigate the tumour suppressor function of p16 in NPC, we tranfected p16-deficient NPC cell line, NPC/HK-1, with a wild-type p16 expression construct, and evaluated growth and tumorigenic properties of the clones stably expressing exogenous p16. Expression of the exogenous wild-type p16 significantly inhibited cell growth by more than 70% when compared to that of the parental and empty vector-transfected cells. This growth inhibition was attributable to a significant proportion of p16-expressing cells arrested at G1 phase in the cell cycle as revealed by flow cytometric analysis. By anchorage-independent colony forming assay, we found that the ability to form colonies in soft agar was highly reduced in cells expressing p16. NPC/HK1 cells expressing functional p16 also showed suppressed tumorigenicity in athymic nude mice. Taken together, our results provide strong evidence for a tumour suppressor role of p16 in NPC.link_to_subscribed_fulltex