Update on Genetic and Clinical Aspects of Primary Hyperparathyroidism: Update on Genetic and Clinical Aspects of Primary Hyperparathyroidism

S. Miedlich, K. Krohn, R. Paschke


Clin Endocrinol. 2003;59(5) 

In This Article

Chromosomal Aberrations and Genetic Abnormalities in Parathyroid Tumours

LOH on chromosome 11q has been described as the most frequently reported genetic abnormality in parathyroid adenomas. Other genetic loci with frequently reported LOH in parathyroid adenomas have been detected on chromosomes 1p, 9p, 11p, 13q and 15q (Cryns et al., 1995; Pearce et al., 1996; Tahara et al., 1996; Agarwal et al., 1998; Inagaki et al., 1998; Palanisamy et al., 1998; Farnebo et al., 1999; Dwight et al., 2000). The large variety of the described chromosomal abnormalities suggests heterogenous genetic defects leading to parathyroid neoplasms.

In addition to the detection of genomic sites with allelic losses, comparative genomic hybridization (CGH) allows identification of regions with chromosomal gains. Chromosomal gains may confer a selective growth advantage upon the cell. Proto-oncogenes, driven by highly active recombinant promoters, could initiate progression through the cell cycle or activate expression of transcription/growth factors. Furthermore, the probability of additional somatic mutations may be increased. In benign parathyroid tumours, chromosomal gains have been repeatedly detected on chromosomes 1, 5, 6, 7, 16 and 19. Furthermore, known oncogenes such as H-ras, K-ras and N-ras(located on chromosomes 11, 1 and 12, respectively) have been investigated for activation by point mutations. In contrast to a frequent detection in other tumours, no ras-mutations could be detected in parathyroid neoplasms (Friedman et al., 1990).

Comparison of the genetic abnormalities in benign and malignant parathyroid neoplasias strongly points to different pathophysiologies. Allelic deletions on chromosome 1p, 4q and 13q as well as gains of 1q, 9q, 16p, 19p and Xq were found significantly more often in parathyroid carcinomas than in adenomas (Kytola et al., 2000). In parathyroid adenomas, LOH on 13q12-14 was associated with aggressive clinical and histopathologic features (Dotzenrath et al., 1996; Pearce et al., 1996). These results denote that allelicloss on chromosome 13q represents an important marker of parathyroid tumours with an aggressive phenotype. LOH on 11q, although one of the most common genetic abnormalities in parathyroid adenomas, has only rarely been detected in parathyroid carcinomas (Agarwal et al., 1998).

In summary, the chromosomal lossesand gains in adenomas and carcinomas suggest distinct underlying pathophysiologies, and render the consecutive development of a parathyroid carcinoma on the basis of benign parathyroid neoplasia unlikely (Mallya & Arnold, 2000). Furthermore, the genetic basis for cell cycle induction in the majority of malignant and benign parathyroid tumours remains to be elucidated.