Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence

• DOI: 10.1016/j.jhep.2019.07.014
• Publication Date: 2019-07-23T15:26:52Z
• Authors: Shao-Lai Zhou; Zheng-Jun Zhou; Zhi-Qiang Hu; Cheng-Li Song; Yi-Jie Luo; Chu-Bin Luo; Hao-Yang Xin; Xin-Rong Yang; Ying-Hong Shi; Zheng Wang; Xiao-Wu Huang; Ya Cao; Jia Fan; Jian Zhou
• Keywords: Male; 0301 basic medicine; China; Carcinoma, Hepatocellular; Liver Neoplasms; Middle Aged; Protein Serine-Threonine Kinases; 3. Good health; 03 medical and health sciences; RUNX1 Translocation Partner 1 Protein; Mutation; Exome Sequencing; Biomarkers, Tumor; Hepatectomy; Humans; Female; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Neoplasm Recurrence, Local; beta Catenin; Signal Transduction

Early recurrence of hepatocellular carcinoma (HCC) after curative resection is common. However, the association between genetic mechanisms and early HCC recurrence, especially in Chinese patients, remains largely unknown.We performed whole-genome sequencing (49 cases), whole-exome (18 deep targeted (115 cases) on 182 primary samples. Focusing WNK2, we used Sanger qPCR to evaluate all coding exons copy numbers that gene an additional 554 We also explored functional effect mechanism WNK2 tumor growth metastasis.We identified 5 genes (WNK2, RUNX1T1, CTNNB1, TSC1, TP53) harboring somatic mutations correlated with overall mutation number loss occurred 5.3% (39/736) 27.2% (200/736), respectively, total 736 Both types variation were associated lower protein levels, higher rates shorter survival. Biofunctional investigations revealed a tumor-suppressor role WNK2: its inactivation led ERK1/2 signaling activation cells, tumor-associated macrophage infiltration, metastasis.Our results delineate genomic events characterize HCCs identify as driver resection.We applied next-generation conducted in-depth analysis carcinomas from patient cohort. The patients resection.