title: Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1.
abstract: 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 β-cells and may provide therapeutic targets for PNETs.
authors: 1] Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [2].
authors: Yanan
authors: Y
authors: Cao
authors: Zhibo
authors: Z
authors: Gao
authors: Lin
authors: L
authors: Li
authors: Xiuli
authors: X
authors: Jiang
authors: Aijing
authors: A
authors: Shan
authors: Jie
authors: J
authors: Cai
authors: Ying
authors: Y
authors: Peng
authors: Yanli
authors: Y
authors: Li
authors: Xiaohua
authors: X
authors: Jiang
authors: Xuanlin
authors: X
authors: Huang
authors: Jiaqian
authors: J
authors: Wang
authors: Qing
authors: Q
authors: Wei
authors: Guijun
authors: G
authors: Qin
authors: Jiajun
authors: J
authors: Zhao
authors: Xiaolong
authors: X
authors: Jin
authors: Li
authors: L
authors: Liu
authors: Yingrui
authors: Y
authors: Li
authors: Weiqing
authors: W
authors: Wang
authors: Jun
authors: J
authors: Wang
authors: Guang
authors: G
authors: Ning
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D002460:Cell Line; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D006801:Humans; D007340:Insulinoma / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010190:Pancreatic Neoplasms / Q000235:genetics*; D051381:Rats; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D050986:YY1 Transcription Factor; C494698:YY1 protein, human