Structural analysis of gene marker loci on chromosomes 10 and 11 in primary and secondary uraemic hyperparathyroidism.

BACKGROUND

The genetic molecular anomalies in patients with primary (I degree) and secondary (II degree) hyperparathyroidism (HPTH) are still largely unknown. In particular, the changes underlying monoclonal growth in the parathyroids of patients with II degree HPTH are not well understood.

METHODS

We screened genomic DNA from a total of 30 patients with I degree HPTH and 29 patients with II degree uraemic HPTH for possible rearrangements or allelic losses of several gene markers located on chromosome 11p near the PTH gene, namely Ha-ras, IGF-2, WT1, and the PTH gene itself. In addition, two other gene markers, PRAD1 (localized on 11q13) and RET (localized on 10q11) were examined for possible structural alterations. Moreover, we used fluorescence in situ hybridization (FISH) which is another technique to detect numerical alterations of chromosome 11.

RESULTS

The results show that one of 13 patients with I degree HPTH (8%) exhibited a rearrangement for the PRAD-1 gene. Loss of heterozygosity of Ha-ras locus was observed in one of 11 uraemic patients with II degree HPTH (9%). Three of 10 patients with I degree HPTH (30%) and one of 7 patients with II degree HPTH (14%) showed an allelic loss of the WT1 gene. No evidence of rearrangement or allelic loss was detected for the IGF-2, PTH or RET genes respectively. Using FISH method, three normal parathyroid gland, six I degree HPTH adenomas and eight II degree HPTH hyperplastic glands from uraemic patients were studied with centromeric probe for chromosome 11. Monosomy 11 was observed in one case of I degree HPTH and in one other case of II degree HPTH.

CONCLUSION

Evidence of loss of heterozygosity for several genes located on human chromosome 11p has been found in a series of parathyroid glands from several patients with I degree and II degree uraemic HPTH, corresponding to monosomy of chromosome 11 in some cases.