The tumor suppressive role of chromosome 3p was demonstrated in various cancers including nasopharyngeal carcinoma (NPC). In this study, we used the elimination test to elucidate the tumor suppressive regions on chromosome 3p21.3 in NPC. Three critical regions were identified from the loss of heterozygosity studies of the microcell hybrids and the corresponding tumor seggregants. These regions overlap with three critical tumor suppressive regions mapped to the 3p21.3 region, which were previously identified in other cancers. We analyzed the tumor suppressive microcell hybrids and their corresponding tumor segregant cell lines by using the cDNA oligonucleotide microarray. One candidate tumor suppressor gene (TSG) mapped to 3p21.3, RIS1, was identified from the cDNA microarray analysis. T...[ Read more ]

The tumor suppressive role of chromosome 3p was demonstrated in various cancers including nasopharyngeal carcinoma (NPC). In this study, we used the elimination test to elucidate the tumor suppressive regions on chromosome 3p21.3 in NPC. Three critical regions were identified from the loss of heterozygosity studies of the microcell hybrids and the corresponding tumor seggregants. These regions overlap with three critical tumor suppressive regions mapped to the 3p21.3 region, which were previously identified in other cancers. We analyzed the tumor suppressive microcell hybrids and their corresponding tumor segregant cell lines by using the cDNA oligonucleotide microarray. One candidate tumor suppressor gene (TSG) mapped to 3p21.3, RIS1, was identified from the cDNA microarray analysis. The 630 kb region at 3p21.3 identified from lung cancer, known as the LUCA region, appears critical for tumor suppression in many cancers and multiple candidate TSGs were mapped to this region. Two candidate TSGs from the LUCA region, BLU/ZMYND10 and SEMA3B, were investigated in more detail. Quantitative RT-PCR shows the down-regulation of BLU/ZMYND10 and SEMA3B was frequently found in NPC cell lines and NPC biopsies. By using the gene inactivation test (GIT), we demonstrated that BLU/ZMYND10 and SEMA3B show tumor suppressive functions in vivo. These results further confirm the tumor suppressive role of chromosome 3p21.3 in NPC. BLU/ZMYND10 and SEMA3B are two candidate TSGs in the 3p21.3 LUCA region, which can functionally suppress tumor growth in vivo.