title: Whole-exome sequencing of duodenal adenocarcinoma identifies recurrent Wnt/β-catenin signaling pathway mutations.
abstract: Genomic alterations of small bowel cancers remain poorly understood due to the rarity of these diseases. In the current study, the authors report the identification of somatic mutations from patients with duodenal adenocarcinoma by whole-exome sequencing.
  
  
  
  Whole-exome sequencing and follow-up analysis were conducted in 12 matched tumor-normal tissue duodenal adenocarcinoma tissue pairs to examine the genetic characteristics of this disease. Somatic mutations (single-nucleotide variants and short insertion/deletions) were obtained and filtered and then searched for recurrently mutated genes and pathways.
  
  
  
  An excess of C-to-T transitions at the CpG dinucleotide was observed in the substitution of bases. The authors identified recurrent mutations in tumor protein p53 (TP53), KRAS, catenin (cadherin-associated protein) β-1 (CTNNB1), AT-rich interactive domain 2 (ARID2), adenomatous polyposis coli (APC), erb-b2 receptor tyrosine kinase 2 (ERBB2), ARID1A, cadherin-related family member 1 (CDHR1), NRAS, Bcl-2-related ovarian killer (BOK), radial spoke head 14 homolog (chlamydomonas) (RTDR1), cell division cycle 27 (CDC27), catalytic subunit of phosphoinositide-3-kinase (PIK3CA), and SMAD family member 4 (SMAD4). Pathway scan indicated that the Wnt signaling pathway, regulation of the actin cytoskeleton pathway, ErbB signaling pathway, and the pathway of focal adhesion were the most extensively affected pathways.
  
  
  
  This genomic characterization of duodenal adenocarcinoma provides researchers with insight into its somatic landscape and highlights the vital role of the Wnt/β-catenin signaling pathway. The study data also indicate that duodenal adenocarcinomas have a genetic resemblance to gastric and colorectal cancers. These discoveries may benefit the future development of molecular diagnosis and personalized therapies. Cancer 2016;122:1689-96. © 2016 American Cancer Society.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Binghua
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Zhengzhou Translational Medicine Research Center, Zhengzhou Sixth People's Hospital, Zhengzhou, Henan Province, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Institute of Biomedical Sciences, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Daizhan
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004379:Duodenal Neoplasms / Q000235:genetics*; D059472:Exome; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009154:Mutation; D017354:Point Mutation; D060449:Wnt Signaling Pathway / Q000235:genetics*
keywords: Bcl-2-related ovarian killer (BOK); Wnt β-catenin signaling pathway; adenocarcinoma; adenomatous polyposis coli (APC); cancer pathways; duodenum; high-throughput nucleotide sequencing; mutation