The ARMC5 gene was discovered by independent workgroups studying benign tumors — so-called adrenal adenomas — in connection with Cushing’s syndrome. In this disease, the body produces too much of the hormone cortisol. Now, for the first time, a mutation of ARMC5 has been characterized as the cause behind the growth of meningeal tumors. The results on this tumor syndrome, obtained by the group of Dr. Patrick May and PD. Dr. Jochen Schneider together with colleagues from Charit� Berlin (Dr. Ulf Elbelt) and the Universities of W�rzburg (Prof. Dr. Bruno Allolio) and Cologne (Dr. Michael Kloth), have been published recently in the Journal of Clinical Endocrinology Metabolism.
Cortisol is an important hormone. It influences many metabolic pathways in the body and has a suppressing effect on the immune system. Accordingly, it is commonly employed as an anti-inflammatory medication. Prolonged, elevated levels of cortisol in the body can lead to obesity, muscular dystrophy, depression and other symptoms. To maintain the correct concentration in the blood, the body has a refined regulation system: Certain areas of the brain produce the hormone corticotropin as a stimulator of cortisol release; the actual formation of cortisol takes place in the adrenal glands. As the concentration of cortisol in the blood rises, the brain reduces the production of corticotropin.
In search of the causes of Cushing’s syndrome, scientists recently encountered certain genetic causes of benign tumors of the adrenal cortex. Growth of these adrenal cortex adenomas is based on a combination of hereditary and spontaneous mutations: It affects people in whom one of two “alternative copies” — one of the so-called alleles — of the ARMC5 gene is mutated from birth. If the second allele of ARMC5 later also undergoes a spontaneous mutation in the adrenal cortex, then the gene no longer functions. “What is interesting is that the failure of ARMC5 has no direct influence on cortisol production. However, because the tumor cells multiply faster than other body cells, and the number of cells in the tumor increases, the blood cortisol level rises in the course of the disease,” says Dr Schneider. Then, the cortisol level in the body rises and ultimately results in the onset of Cushing’s syndrome.
When other scientific workgroups discovered that further benign tumors — in this case meningeal tumors — occur more often in ARMC5-Cushing families, the group of Patrick May and Jochen Schneider sequenced the ARMC5 gene and studied it using bioinformatic techniques. “We demonstrated for the first time, in a patient with an adrenal cortex tumor and simultaneously a meningeal tumor, that somatic, that is non-hereditary, ARMC5 mutations are present in both tumors. This observation suggests that ARMC5 is a true tumor-suppressor gene.”
It must now be explored, Schneider continues, to what extent patients with adrenal cortex tumors ought to be screened for simultaneous presence of meningioma, and in which other types of tumor ARMC5 mutations are responsible for tumor growth: “Building upon that, we can learn whether the gene and the metabolic pathways it influences offer new approaches for treating the tumor syndrome.”
source : http://www.sciencedaily.com/releases/2014/10/141013090455.htm