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Int J Biol Sci 2014; 10(9):957-965. doi:10.7150/ijbs.9773

Research Paper

KRAS and DAXX/ATRX Gene Mutations Are Correlated with the Clinicopathological Features, Advanced Diseases, and Poor Prognosis in Chinese Patients with Pancreatic Neuroendocrine Tumors

Fei Yuan3*, Min Shi1*, Jun Ji1, Hailong Shi1, Chenfei Zhou1, Yingyan Yu1, Bingya Liu1, Zhenggang Zhu1,2, Jun Zhang1,2✉

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;
3. Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China.
*Equal contribution.

Abstract

Background and Aim: 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.

Conclusion: 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.

Keywords: pancreatic neuroendocrine tumor, gene mutation, prognosis, KRAS, DAXX/ATRX.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Yuan F, Shi M, Ji J, Shi H, Zhou C, Yu Y, Liu B, Zhu Z, Zhang J. KRAS and DAXX/ATRX Gene Mutations Are Correlated with the Clinicopathological Features, Advanced Diseases, and Poor Prognosis in Chinese Patients with Pancreatic Neuroendocrine Tumors. Int J Biol Sci 2014; 10(9):957-965. doi:10.7150/ijbs.9773. Available from http://www.ijbs.com/v10p0957.htm