Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of patients with primary hyperparathyroidism (HPT), but a relatively higher incidence has been reported in Italy and Japan. The etiology of the tumour remains unclear, but molecular analysis studies have hypothesised the involvement of mutations of several genes in the pathogenesis of PC, including the oncogene cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53 tumour suppressor gene. The clinical presentation of patients with PC is mainly related to the increased secretion of PTH rather than to the tumour burden. The pre-operative diagnosis of malignancy is very difficult to obtain, and, thus, intra-operative recognition of PC is mandatory. However, reliable signs of malignancy are rarely detectable. Probably, only vascular invasion, that correlates with tumour recurrence and metastases, should be considered useful in confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used to aid in the definitive diagnosis. The en bloc resection of the tumour, together with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding any capsular rupture of the mass, represents the gold standard of surgical treatment of patients. Although the PC has traditionally been considered as a radioresistant tumour, there are some retrospective data holding a possible benefit from post-operative irradiation. No cytotoxic regimen with proven efficacy is currently available for patients with PC, but since hypercalcemia is ultimately the most frequent cause of death, several studies have suggested the usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate), calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey reports an overall five- and ten-year survival rate of 85% and 49%, respectively. However, it is very difficult to predict the clinical behaviour of patients with PC and probably the ultimate prognosis depends on successful resection of the tumour at the initial surgery.
 ...
PMID:Parathyroid cancer: etiology, clinical presentation and treatment. 1721 44

Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level, and the deleterious effects of hypercalcaemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested potential roles for the tumour suppressor MEN1 and proto-oncogene RET in benign parathyroid tumourigenesis, while the tumour suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumour specimens were analysed using high-throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well-characterized cancer genes such as mTOR, MLL2, CDKN2C, and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumours revealed loss of PIK3CA activating mutation during the evolution of the tumour from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of the short arm of chromosome 1, along with somatic missense and truncating mutations in CDKN2C and THRAP3, respectively, provides new evidence for the potential role of these genes as tumour suppressors in parathyroid cancer. The key somatic mutations identified in this study can serve as novel diagnostic markers as well as therapeutic targets.
 ...
PMID:Complete genomic landscape of a recurring sporadic parathyroid carcinoma. 2361 56