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Geme mutation potential target for diagnosis, treatment of insulinoma

Date:
December 11, 2013
Source:
BGI Shenzhen
Summary:
Chinese researchers have identified the recurrent T372R mutation in the transcription factor YY1 (Yin Yang 1) are related with insulinoma oncogenesis, implicating a potential marker for the diagnosis and treatment of functional pancreatic neuroendocrine tumors (PNETs).

Chinese researchers from Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, BGI and other institutes identified the recurrent T372R mutation in the transcription factor YY1 (Yin Yang 1) are related with insulinoma oncogenesis, implicating a potential marker for the diagnosis and treatment of functional pancreatic neuroendocrine tumors (PNETs). The latest study was published online in Nature Communications.

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Pancreatic neuroendocrine tumors are classified into functional and nonfunctional tumors by hormone secretion and clinical symptoms. Functional PNETs are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycemia. The major genetic alterations in insulinomas are still unknown.

In this study, researchers identified T372R mutation in YY1 by whole exome sequencing of 10 sporadic insulinomas samples. It is noteworthy that the T372R mutation was the first reported in public available databases such as 1,000 Genomes and dbSNP database. YY1 is a multifunctional protein, which takes part in regulating normal physiological progress such as development, differentiation, replication and cell proliferation. It also plays an important role in regulating insulin and insulin-like growth factor (IGF) signaling that is crucial for pancreatic β-cell survival and insulin secretion.   

Subsequently, researchers validated T372R mutation in 103 additional insulinomas samples. The results showed that 31 in 103 cases had the T372R mutation, providing evidence to support that T372R mutation is a pathogenic factor of insulinoma. In addition, they found T372R mutation could enhance the transcriptional activity of YY1. The mTOR inhibitor which has been approved to use for cancer treatment also can regulate the transcriptional activity of YY1.

Lin Li, Project Manager from BGI, said: "In this study, we conducted whole exome sequencing on sporadic insulinomas, and found the hotspot mutations of T372R in 30% insulinomas. The findings not only contribute new diagnostic and medical therapies of PNETs, but also provide new insights into diabetes studies."


Story Source:

The above story is based on materials provided by BGI Shenzhen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yanan Cao, Zhibo Gao, Lin Li, Xiuli Jiang, Aijing Shan, Jie Cai, Ying Peng, Yanli Li, Xiaohua Jiang, Xuanlin Huang, Jiaqian Wang, Qing Wei, Guijun Qin, Jiajun Zhao, Xiaolong Jin, Li Liu, Yingrui Li, Weiqing Wang, Jun Wang, Guang Ning. Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1. Nature Communications, 2013; 4 DOI: 10.1038/ncomms3810

Cite This Page:

BGI Shenzhen. "Geme mutation potential target for diagnosis, treatment of insulinoma." ScienceDaily. ScienceDaily, 11 December 2013. <www.sciencedaily.com/releases/2013/12/131211104610.htm>.
BGI Shenzhen. (2013, December 11). Geme mutation potential target for diagnosis, treatment of insulinoma. ScienceDaily. Retrieved November 1, 2014 from www.sciencedaily.com/releases/2013/12/131211104610.htm
BGI Shenzhen. "Geme mutation potential target for diagnosis, treatment of insulinoma." ScienceDaily. www.sciencedaily.com/releases/2013/12/131211104610.htm (accessed November 1, 2014).

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