title: KRAS and DAXX/ATRX gene mutations are correlated with the clinicopathological features, advanced diseases, and poor prognosis in Chinese patients with pancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  Pancreatic neuroendocrine tumor (pNET) is a clinically rare and heterogeneous group of tumors; its pharmacogenetic characteristics are not fully understood. This study was designed to examine the relationship between key gene variations and disease development and prognosis among Chinese patients with pNET.
  
  
  METHODS
  Various pNET associated genes such as DAXX/ATRX, KRAS, MEN1, PTEN, TSC2, SMAD4/DPC, TP53 and VHL were analyzed in high-throughput sequencing. The links between the gene mutations and the clinicopathological features and prognosis of the patients were determined.
  
  
  RESULTS
  The somatic mutation frequencies of the DAXX/ATRX, KRAS, MEN1, mTOR pathway genes (PTEN and TSC2), SMAD4/DPC, TP53, and VHL in Chinese pNET patients were 54.05%, 10.81%, 35.14%, 54.05%, 2.70%, 13.51%, and 40.54%, respectively, while the same figures in Caucasians pNET patients were 43%, 0%, 44%, 15%, 0%, 3%, and 0%, respectively. The numbers of mutated genes were from 0 to 6; 4 patients with more than 3 mutated genes had higher proliferation (Ki-67) index or nerve vascular invasion or organ involvement, but only 9 of 27 patients with 3 or few mutated genes had such features. Mutations in KRAS and DAXX/ATRX, but not other genes analyzed, were associated with a shortened survival.
  
  
  CONCLUSIONS
  The mutation rates of these genes in Chinese pNET patients are different from those in Caucasians. A higher number of gene mutations and the DAXX/ATRX and KRAS gene mutations are correlated with a poor prognosis of patients with pNET.
authors.affiliation: 3. Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yuan
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Hailong
authors.initials: H
authors.lastname: Shi
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Chenfei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China; ; 2. Department of Clinical Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: 1. Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China; ; 2. Department of Clinical Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China;
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D000075924:X-linked Nuclear Protein; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C117307:KRAS protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: DAXX/ATRX.; KRAS; gene mutation; pancreatic neuroendocrine tumor; prognosis