Loss of heterozygosity in sporadic parathyroid tumours: involvement of chromosome 1 and the MEN1 gene locus in 11q13.

OBJECTIVE Hyperparathyroidism (HPT) is a common endocrine disorder. Several loci of genetic interest have been identified in parathyroid tumours, incl uding the MEN1 gene locus at 11q13; the HPT-JT region at 1q21-q32; and a pu tative tumour suppressor gene on 1p. We analysed these intervals, which har bour known genes or putative loci associated with familial hyperparathyroid ism, in order to clarify the involvement of the respective regions in parat hyroid tumourigenesis. DESIGN We performed loss of heterozygosity (LOH) studies on 33 sporadic par athyroid tumours using a PCR based technique. A total of 22 microsatellite markers were used to analyse loci at 11q13, 1q21-q32 and Ip, Ten markers lo cated distal on Ip, eight markers encompassed the HPT-JT region at 1q21-q32 and four markers surrounded the MEN1 gene locus at 11q13. MEN1 mutations w ere screened for using Single Strand Conformation polymorphism analysis (SS CP) and automated sequencing of SSCP variants. PATIENTS Thirty-three parathyroid glands and the corresponding blood sample s were obtained from 33 patients (26 females and seven males) who underwent parathyroidectomy for primary hyperparathyroidism. RESULTS Loss of heterozygosity was detected in 13 of 33 (39%) cases at 11q1 3, 6 of 33 (18%) cases at 1p, and in three of 33 (9%) cases at 1q (in conju nction with 1p loss). Only one of the 18 tumours in which LOH was detected, showed LOH at both chromosome 1 and chromosome 11. Additionally, those tum ours found to exhibit LOH at 11q13 were screened for MEN1 mutations using s ingle strand conformation polymorphism analysis (SSCP) and automated sequen cing. Nine novel somatic mutations were found on the remaining allele in 13 (69%) tumours. CONCLUSIONS This study consolidates the role of multiple loci in the pathog enesis of sporadic parathyroid tumours, The results indicate that there are at least two genetic loci involved in sporadic parathyroid tumourigenesis on chromosome 1, one of which has been linked to the distinct familial para thyroid condition, hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The hi gh frequency of loss of heterozygosity at 1p suggests the presence of a tum our suppressor at this locus.