Examinations of genetic alterations in adrenal tumors: DNA, RNA and protein studies
Informations
- Funding country
Hungary- Acronym
- -
- URL
- -
- Start date
- 1/1/2009
- End date
- 12/31/2011
- Budget
- 39,115 EUR
Fundings
| Name | Role | Start | End | Amount |
|---|---|---|---|---|
| Postdoctoral Programme | Grant | 1/1/2009 | 12/31/2011 | 39,115 EUR |
Abstract
Adrenal tumours are frequently discovered during abdominal imaging (estimated incidence is between 0.35-4.36% in the general population). These tumors represent serious diagnostic and therapeutic problems. Majority of these tumors are non-functioning, benign adrenal adenomas but adrenocortical carcinomas can also be found. 9-15% of tumors involve both adrenals. The metabolic syndrome, hypertension, obesity, diabetes mellitus, osteoporosis and abnormalities of the hypothalamic-pituitary-adrenal are common findings in these patients. These clinical observations suggest that systemic effects, such as genetic alterations, could play a role in their pathogenesis. In my earlier studies I identified mutations of the CYP21A2 and the glucocorticoid receptor gene in patients with both bilateral and unilateral hormonally inactive adrenal adenomas. Pathogenic role of mutations of RET and vhl genes in adrenal medullary tumors is well-known. My current proposal aims to evaluate the genetic variants of nuclear (CYP21A2, TP53, vhl, RET, SDH) and mitochondrial encoded genes on germline and in tumor tissue as well. Current data from literature support the role of mitochondria in tumorigenesis, to date only in adrenal medullary tumors have been identified germline mutations of genes encoding the subunits of succinate dehydrogenase enzyme. Complex analysis of the clinico-pathologial, hormone laboratory and genetic data obtained from patients with adrenal tumors will proveide new genotype-phenotype associations. Beside DNA examinations, the functional role of genetic variants will be evaluted on gene transcription and protein level, respectively. Analysis of genetic variants of genes encoding the mitochondrial electron transport chain and steroid biosynthesis will reveal new pathomechanisms involved in adrenal tumorigenesis.