Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma

Scientific Reports
Ming-Hui YangYi-Ming Arthur Chen

Abstract

Characterized with a high recurrence rate and low detection rate, prevention is the best approach to reduce mortality in hepatocellular carcinoma (HCC). The overexpression of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) is observed in various tumors, including HCC; and the frequent PREX2 mutations in melanoma are associated with invasiveness. We sought to identify somatic mutations and the functional changes in mutational signatures of PREX2. Genomic DNA sequencing was performed in 68 HCC samples with three types of hepatitis viral infection status: HBs Ag-positive, anti-HCV Ab-positive, and negative for any hepatitis B or C markers. Stabilities and interactions of proteins as well as cell proliferation and migration were evaluated. Fourteen non-silent point mutations in PREX2 were detected, with 16 of 68 HCC patients harboring at least one non-silent mutation. All mutant forms of PREX2, except for K400f, had an extended half-life compared with wild-type PREX2. Moreover, only the half-life of S1113R was twice that of the wild-type. PREX2 mutant-S1113R also promoted migration and activated the AKT pathway as well as impaired HectH9-mediated ubiquitination. Our study identified a gain-of-functi...Continue Reading

References

Aug 12, 2004·FEBS Letters·Hans RosenfeldtJ Silvio Gutkind
Aug 12, 2004·FEBS Letters·Sarah DonaldHeidi C E Welch
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Aug 29, 2009·Science·Wei-Lei YangHui-Kuan Lin
Jan 17, 2012·The Biochemical Journal·Mark A BarberHeidi C E Welch
May 25, 2012·Nature·Michael F BergerLevi A Garraway
Nov 28, 2012·Expert Review of Anticancer Therapy·Amanda PsyrriGeorge Dimitriadis
Jun 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Atanasio Pandiella, Juan Carlos Montero
Jul 23, 2013·PLoS Computational Biology·Umadevi PailaAaron R Quinlan
Dec 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Cindy HodakoskiRamon Parsons
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Feb 27, 2015·Nature·Nicola WaddellSean M Grimmond
Apr 2, 2015·Science Signaling·Sarah M MenseRamon Parsons
Feb 17, 2017·International Journal of Cancer. Journal International Du Cancer·Chung-Hsien LiYi-Ming Arthur Chen
May 26, 2017·Cancer·Bobby Y ReddyHensin Tsao
Jul 16, 2017·Biochemical Society Transactions·Nuthasuda SrijakotreChristina A Mitchell
Aug 8, 2017·Nature·Dan R RobinsonArul M Chinnaiyan

❮ Previous
Next ❯

Citations

Apr 4, 2021·International Journal of Molecular Sciences·Eugene ChoiSuk Kyeong Lee
Jun 7, 2019·Toxicology and Applied Pharmacology·Marcelo ChenYi-Ming Arthur Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
nucleotide exchange
Illumina sequencing
ubiquitination
co-IP
transfections
Immunoprecipitation
protein assay

Software Mentioned

GEMINI
Dolphin View Band Tool
SPSS
CLC Genomics Workbench

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.