STRUCTURAL-ANALYSIS OF GENE MARKER LOCI ON CHROMOSOME-10 AND CHROMOSOME-11 IN PRIMARY AND SECONDARY UREMIC HYPERPARATHYROIDISM

Background. The genetic molecular anomalies in patients with primary ( I degrees) and secondary (II degrees) hyperparathyroidism (HPTH) are s till largely unknown. In particular, the changes underlying monoclonal growth in the parathyroids of patients with II degrees HPTH are not w ell understood. Methods. We screened genomic DNA from a total of 30 pa tients with I degrees HPTH and 29 patients with II degrees uraemic HPT H for possible rearrangements or allelic losses of several gene marker s located on chromosome 11p near the PTH gene, namely Ha-ras, IGF-2, W T1, and the PTH gene itself. In addition, two other gene markers. PRAD 1 (localized on 11q13)and RET(localized on 10Q11) were examined for po ssible structural alterations. Moreover, we used fluorescence in situ hybridization (FISH) which is another technique to detect numerical al terations of chromosome 11. Results. The results show that one of 13 p atients with I degrees HPTH (8%) exhibited a rearrangement for the PRA D-1 gene. Loss of heterozygosity of Ha-ras locus was observed in one o f 11 uraemic patients with II degrees HPTH (9%). Three of 10 patients with I degrees HPTH (30%) and one of 7 patients with II degrees HPTH ( 14%) showed an allelic loss of the WT1 gene. No evidence of rearrangem ent or allelic loss was detected for the IGF-2,, PTH or RET genes resp ectively. Using FISH method, three normal parathyroid glands, six I de grees HPTH adenomas and eight II degrees HPTH hyperplastic glands from uraemic patients were studied with centromeric probe for chromosome 1 1. Monosomy 11 was observed in one case of I degrees HPTH and in one o ther case of II degrees HPTH. Conclusion. Evidence of loss of heterozy gosity for several genes located on human chromosome lip has been foun d in a series of parathyroid glands from several patients with I degre es and II degrees uraemic HPTH, corresponding to monosomy of chromosom e 11 in some cases.