In vitro hyperdiploidy in a family with nasopharyngeal cancer.

In this in vitro study of 28 members of a family with nasopharyngeal cancer (NPC) and nasopharyngeal angiofibromas (NPA) in consecutive generations, in vitro hyperdiploidy, (IVH) in dermal fibroblast cultures was associated with NPC in 2 affected members, NPA in 4 affected members, and 4 of 16 members considered to be at increased genetic risk for these tumors. None of the six controls, all spouses, had IVH. As IVH has been shown to be associated with high specificity (approximately 99%) with other heritable single tumors, IVH appeared to be a potential biomarker also for genetic predisposition for NPC. As NPC and NPA did not occur in a single affected family member, any association other than with IVH has not been established. IVH may be the in vitro expression of a gene/genes conveying tumor proneness per se, or it may determine tissue specificity of tumor pathology. As cellular hyperdiploidy has been considered to convey genomic instability, chromosome instability in numerically normal (diploid) and altered (tetraploidy and hyperdiploid) dermal fibroblasts from two NPC-affected members and two control spouses were evaluated by a parameter of chromosome stability--the frequency of sister chromatid exchanges (SCE) per cell. Irrespective of donor source, the diploid and tetraploid fibroblasts exhibited little evidence of chromosome instability, whereas there was a statistically significant difference in the mean frequency of SCE/cell between hyperdiploid and diploid cells in cultures derived from NPC-affected members (p less than 0.01).