Objective: To further refine the extent of deletion on chromosome 9p21-22 in nasopharyngeal carcinoma (NPC) and provide evidence for discovering new tumor suppressor gene. Methods: Loss of heterozygosity (LOH) on chromosome 9p21-22 was analyzed in 25 paired blood and tumor samples by using 11 high-density microsatellite polymorphic markers. Results: 17 of 25 cases (68.0%) showed LOH at one or more loci. Higher frequencies of LOH were found at four loci: D9S161 (35.0%), D9S1678 (31.5%), D9S263 (33.3%) and D9S1853 (33.3%), where 6 cases had a contiguous stretch of allelic loss. Conclusion: The minimal common region of deletion might be defined between D9S161 and D9S1853 (estimated about 2.7 cM in extent) at 9p21.1, suggesting that inactivation of one or more tumor suppressor genes located in this region may be an important step in NPC.
Bibliographical noteFunding Information:
Previous studies have showed that Epstein-Barr virus (EBV) infection, certain environmental factors and genetic factors were found to be closely associated with nasopharyngeal carcinoma. The rates of NPC in southern China and Southeast Asia are 25 times higher than that of Received April 10, 2000, accepted July 17, 2000 This work was supported by a grant from the National "863" Project of China (No. 102-10-01-05). Correspondence to: LI Gui-yuan, Cancer Research Institute, Hunan Medical University, No. 88, Xiangya Road, Changsha 410078, Hunan, China; Phone: (0086-731)-4805446; Fax: (0086-731)-4805383; E-mail: firstname.lastname@example.org in western countries. The statistic analysis revealed 5%-10% NPC patients have family history, there, genetic susceptibility might be an important factor in the pathogenesis of NPC. Unfortunately the alterations of common tumor suppressor genes are rare in NPC. Previous cytogenetic and molecular genetic studies have showed that loss of heterozygosity (LOH) on chromosome 9p21-22 is one of the most frequent genetic alterations in NPC and in many common sporadic cancers which suggested that there may be more than one TSG on 9p21-22. The pl6/MTS1 gene located at 9p21.has been considered a putative tumor suppressor gene at this region. Although homozygous deletion and point mutations of p l6/MTS1 occur frequently in a variety of human tumor cell lines, corresponding evidence of the same alternations in primary NPC samples is less common. To further precisely the refine extent of deletion on chromosome 9p21-22 in NPC, in this study, we performed loss of heterozygosity analysis on chromosome 9p21-22 in 25 paired blood and tumor samples using 11 high-density microsatellite polymorphic markers.
- Chromosome 9p21-22
- Loss of heterozygosity
- Nasopharyngeal carcinoma
- Tumor suppressor gene