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- Title
Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway.
- Authors
Li, Maolan; Zhang, Zhou; Li, Xiaoguang; Ye, Junyi; Wu, Xiangsong; Tan, Zhujun; Liu, Chang; Shen, Baiyong; Wang, Xu-An; Wu, Wenguang; Zhou, Daizhan; Zhang, Di; Wang, Ting; Liu, Bingya; Qu, Kai; Ding, Qichen; Weng, Hao; Ding, Qian; Mu, Jiasheng; Shu, Yijun
- Abstract
Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR) < 0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P = 0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.
- Subjects
GALLBLADDER cancer; CARCINOMA; CANCER genetics; BILIARY tract cancer; MEDICAL genetics
- Publication
Nature Genetics, 2014, Vol 46, Issue 8, p872
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.3030