Exome Capture Sequencing of Adenoma Reveals Genetic Alterations in Multiple Cellular Pathways at the Early Stage of Colorectal Tumorigenesis

• DOI: 10.1371/journal.pone.0053310
• Publication Date: 2013-01-03T01:05:05Z
• Authors: Donger Zhou; Liu Yang; Liangtao Zheng; Weiting Ge; Dan Li; Yong Zhang; Xueda Hu; Zhibo Gao; Jinghong Xu; Yanqin Huang; Hanguang Hu; Hang Zhang; Hao Zhang; Mingming Liu; Huanming Yang; Lei Zheng; Shu Zheng
• Keywords: Nonsynonymous substitution; Colorectal adenoma; Exome

Most of colorectal adenocarcinomas are believed to arise from adenomas, which premalignant lesions. Sequencing the whole exome adenoma will help identifying molecular biomarkers that can predict occurrence adenocarcinoma more precisely and understanding pathways underlying initial stage tumorigenesis. We performed capture sequencing normal mucosa, tissues same patient sequenced identified mutations in additional 73 adenomas 288 adenocarcinomas. Somatic single nucleotide variations (SNVs) were both by comparing with control patient. 12 nonsynonymous somatic SNVs 42 adenocarcinoma. these including OR6X1, SLC15A3, KRTHB4, RBFOX1, LAMA3, CDH20, BIRC6, NMBR, GLCCI1, EFR3A, FTHL17 newly reported adenomas. Functional annotation mutated genes showed multiple cellular Wnt, cell adhesion ubiquitin mediated proteolysis altered genetically genetic alterations persist CDH20 LAMA3 while NRXN3 COL4A6 patient, suggesting for first time pathway occur as early adenoma. Thus, comparison genomic between provides us a new insight into events governing step