Navigation Links
Key genetic mutations could be new hope for adrenocortical tumor patients

April 3, 2014, Shenzhen, China - Chinese researchers from Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, BGI, and other institutions have discovered that the activating hotspot L205R mutation in PRKACA gene was closely associated with adrenocortical tumors (ACTs), and the relationship of recurrently mutated DOT1L and CLASP2 with ACTs' other subtypes. The latest study published online in Science opens a new insight into diagnosis and treatment of Adrenal Cushing's syndrome.

Adrenal Cushing's syndrome results from autonomous production of cortisol (ACTH-independent) from adrenocortical tumors (ACTs), which may lead to a series of metabolic disorders such as obesity, glucose intolerance and hypertension. However, the genetic architecture of Adrenal Cushing's syndrome remains largely uncharacterized, hampering the development of diagnostic and therapeutic approaches for Cushing's syndrome.

In this study, researchers performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), and adrenocortical oncocytoma (ADO). They found there was a hotspot L205R mutation in PRKACA gene, and two novel mutated genes that have never been reported: One is DOT1L, which may contribute the tumorigenesis of AIMAH; the other is HDAC9, which would be responsible for ADOs.

In the large-scale validation stage, researchers found that L205R mutation was only found in the ACTs, and located in the highly conserved functional domain-P+1 loop of PKA catalytic subunit-plays an important role in the combination of kinase and substrate. The further molecular and cell function validation proved that L205R mutation caused the increase of protein activity and enhanced the catalytic capability of the phosphorylation, and promoted the occurrence of tumor and the production of steroid by substrate phosphorylation.

Yanan Cao, Endocrinologist from Rui-Jin Hospital, said,"ACTs and Cushing's syndrome belong to one important kind of diseases in endocrine metabolic disorders. Our study revealed several key mutated genes closely associated with adrenocortical tumors. Furthermore, we systematically analyzed the function of L205R mutation by structure and molecular biology technologies, laying a solid foundation for developing new treatment strategies for Adrenal Cushing's syndrome."

Minghui He, Project Manager of BGI, said, "Using high-throughput sequencing and bioinformatics technologies, we characterized mutation landscape of adrenocortical tumor, and found L205R mutation in PRKACA gene was closely associated with adrenocortical tumors. These findings provide new insights into the clinical diagnosis and treatment of adrenocortical tumors."


Contact: Jia Liu
BGI Shenzhen

Related biology news :

1. Examination of a cave-dwelling fish finds a possible genetic link to human disorders
2. Xiangling Wang, M.D., Ph.D. receives Pfizer/ACMG Foundation Clinical Genetics Fellowship
3. Genetic markers may predict when people with heart disease are likely to have a heart attack
4. Erasing a genetic mutation
5. Genetic mutations warn of skin cancer risk
6. Drilling into the trends in genetics and epigenetics of aging and longevity
7. Faster genetic testing method will likely transform care for patients with breast cancer
8. Genetics can explain why infections can trigger rheumatoid arthritis
9. Certain genetic variants may put bladder cancer patients at increased risk of recurrence
10. MRI reveals genetic activity
11. UT Southwestern ob/gyn researchers studying genetic factors in premature births
Post Your Comments:
(Date:5/16/2016)... , May 16, 2016   EyeLock LLC , ... announced the opening of an IoT Center of Excellence ... and expand the development of embedded iris biometric applications. ... level of convenience and security with unmatched biometric accuracy, ... identity aside from DNA. EyeLock,s platform uses video technology ...
(Date:5/9/2016)... DUBAI , UAE, May 9, 2016 ... choice when it comes to expanding freedom for high ... Even in today,s globally connected world, there ... online conferencing system could ever duplicate sealing your deal ... are obtaining second passports by taking advantage of citizenship ...
(Date:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published today in ... patient who developed lymphedema after being treated for breast cancer benefitted from an injection ... for dealing with this debilitating, frequent side effect of cancer treatment. , ...
(Date:6/23/2016)... , June 23, 2016 ... Hematology Review, 2016;12(1):22-8 ... , the peer-reviewed journal from touchONCOLOGY, Andrew ... escalating cost of cancer care is placing an ... result of expensive biologic therapies. With the patents ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® Inc. ... a free webinar on Performing Quality Investigations: Getting to Root Cause. ... at no charge. , Incomplete investigations are still a major concern to the ...
(Date:6/23/2016)... 23, 2016 adds ... to its pharmaceuticals section with historic and forecast ... much more. Complete report on the ... profiling 15 companies and supported with 261 tables ... . The Global Cell Culture ...
Breaking Biology Technology: