期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3810
关键词
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资金
- Natural Science Foundation of China [30900702, 81170739, 81130016, 81270859]
- Guangdong Innovative Research Team Program [2009010016]
- Shanghai Committee of Science and Technology [11140900501]
- 'Chen Guang' project, Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [11CG18]
Functional pancreatic neuroendocrine tumours (PNETs) are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycaemia. The major genetic alterations in sporadic insulinomas are still unknown. Here we identify recurrent somatic T372R mutations in YY1 by whole exome sequencing of 10 sporadic insulinomas. Further screening in 103 additional insulinomas reveals this hotspot mutation in 30% (34/113) of all tumours. T372R mutation alters the expression of YY1 target genes in insulinomas. Clinically, the T372R mutation is associated with the later onset of tumours. Genotyping of YY1, a target of mTOR inhibitors, may contribute to medical treatment of insulinomas. Our findings highlight the importance of YY1 in pancreatic beta-cells and may provide therapeutic targets for PNETs.
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