Alterations on chromosome 3 in endemic and nonendemic nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is endemic in parts of southern China and is etiologically associated with Epstein-Barr virus (EBV) infection as well as other dietary and environmental factors. Loss of heterozygosity (LOH) on chromosome 3p has been described in NPC from the endemic region. In this study, tumors originating from both the NPC nonendemic area of northern China and the endemic area in southern China were analyzed for LOH at 8 microsatellite markers on chromosome 3. Allele loss was detected at D3S1300 in 3p14.2 in more than 50% of tumors from both the endemic and nonendemic areas, suggesting that LOH at this locus probably does not account for the endemicity of NPC in southern China. The 3p14.2 region encompasses FHIT, a candidate tumor suppressor gene previously shown to be rearranged in several NPC cell lines. In this study, analysis of FHIT gene structure and transcription in primary tumors did not support a role for FHIT in NPC. However, the high frequency of allele loss at 3p14.2 in NPC from endemic and nonendemic regions supports the possibility that an important tumor suppressor gene other than FHIT complements EBV transformation and resides in this region.