Allelic loss in clinically and screening-detected primary hyperparathyroidism.
OBJECTIVE
Parathyroid adenomas frequently harbour deletions of genomic DNA at chromosome regions 1p, 6q and 11q. In this study we related clinical characteristics in 56 patients with primary hyperparathyroidism (pHPT) to loss of heterozygosity (LOH) in these chromosome regions.


METHODS
LOH analysis was performed on 56 sporadic parathyroid tumours using a total of 18 microsatellite markers for chromosome regions 1p, 6q and 11q. LOH was identified, for either radioactive or fluorescent labelled markers, as total absence or reduction of > or = 50% of the signal intensity of an allele in the tumour DNA vs. constitutional DNA.


METHODS
Twenty-one of the patients were recruited by a population-based screening for pHPT and the remaining pHPT patients were gathered from routine clinical practice.


RESULTS
In total, 27%, 23% and 23% of the tumours showed LOH at 1p, 6q and 11q, respectively. LOH at both 1p and 11q was more common in the screening-detected pHPT patients compared to those recruited from clinical practice (38% vs. 20%; P = 0.02 and 43% vs. 11%; P = 0.001, respectively), while allelic loss at 6q was more prevalent in the latter group (11% vs. 31%; P = 0.001). No apparent relationships between LOH at 1p, 6q, and 11q and clinical characteristics, such as glandular weight, serum levels of PTH or calcium, were demonstrated. Moreover, additional LOH analysis of chromosome 1p suggested a putative parathyroid tumour suppressor gene(s) in the region between markers DS214 and D1S503, spanning approximately 6 cM.


CONCLUSIONS
A high frequency of LOH at 1p and 11q in tumours of screening-detected pHPT patients is intriguing, and may suggest that inactivation of known (the MEN1 gene) and putative tumour suppressor genes at these chromosomal regions is associated with a more benign disease.
Correa
Pamela
P
Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Pamela.Correa@kirurgi.uu.se
Juhlin
Christofer
C
Rastad
Jonas
J
Akerström
Göran
G
Westin
Gunnar
G
Carling
Tobias
T
D000368:Aged; D016009:Chi-Square Distribution; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000175:diagnosis / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008403:Mass Screening; D008875:Middle Aged