Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients

• DOI: 10.1186/s12967-019-1867-6
• Publication Date: 2019-04-03T12:03:11Z
• Authors: Chunchao Zhu; Qin Yang; Jia Xu; Wenyi Zhao; Zizhen Zhang; Danhua Xu; Yeqian Zhang; Enhao Zhao; Gang Zhao
• Keywords: Adult; Male; 0301 basic medicine; DNAH mutation; Chemotherapy response; Adenocarcinoma; Biomarkers, Pharmacological; Disease-Free Survival; Cohort Studies; 03 medical and health sciences; Stomach Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Exome Sequencing; Biomarkers, Tumor; Humans; Aged; Aged, 80 and over; Research; R; Dyneins; TCGA; Middle Aged; Prognosis; 3. Good health; Treatment Outcome; Multigene Family; Mutation; Medicine; Female; Gastric cancer

The dynein axonemal heavy chain (DNAH) family of genes encode the chain, which is involved in cell motility. Genomic variations DNAH members have been frequently reported diverse kinds malignant tumors. In this study, we analyzed genomic database to evaluate mutation status gastric adenocarcinoma and further identified significance mutant as effective molecular biomarkers for predicting chemotherapy response cancer patients. We clinical data patients published Cancer Genome Atlas (TCGA) project. Data on response, overall survival (OS) chemotherapy-free were retrieved. Then, verified results via targeted sequencing with similar characteristics but different chemotherapeutic outcomes. total, 132 undergoing treatment from TCGA included our study. Somatic mutations all 13 associated responses. Compared wild-type (n = 59), a significantly higher proportion those 73) (55.9% vs 80.8%) responded (P 0.002). Moreover, correlated better OS 0.027), fluoropyrimidine-free 0.048) platinum-free 0.014). was an independent risk factor 0.015), 0.015) 0.011). somatic 27 (42.2%) 64 stage III receiving fluoropyrimidine-based by exon strict screening conditions. own cohort, 32) than had good prognosis (OS > 48 months) (70.4% 35.1%) 0.005). Dynein gene contribute positively sensitivity