Homologs of the recently described mouse pro genes, that transfer sensitivity to promotion of neoplastic transformation by tumor promoters, have been cloned from a genomic library of the human nasopharyngeal carcinoma (NPC) cell line CNE2.
The proto-oncogene c-fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein-Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV-infected tissues was analyzed on Northern blots to determine if c-fgr is expressed during lympho-proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus.
The proto-oncogene c-fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein-Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV-infected tissues was analyzed on Northern blots to determine if c-fgr is expressed during lympho-proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus.
As the soluble form of the Blast2/CD23 protein possesses growth factor activity associated with EBV-induced B-cell immortalization, these results suggest a possible role for this molecule in the pathogenesis of NPC.
However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions.
However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions.
Our results seem to indicate that mutations in the p53 gene contribute to a significant number of cases of the head and neck tumors including 20% of nasopharyngeal carcinoma biopsies.
Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus.
We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases.
Epstein-Barr virus (EBV) genome-positive nasopharyngeal carcinomas (NPCs) regularly express the virus-coded nuclear antigen EBNA1, but not other EBNAs, and a subset of tumors also appear to be latent membrane protein LMP1 positive; the status of NPCs with respect to a second virus-coded latent membrane protein LMP2 is unknown.