title: A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas.
abstract: Previous genetic studies on colorectal carcinomas (CRC) have identified multiple somatic mutations in four candidate pathways (TGF-β, Wnt, P53 and RTK-RAS pathways) on populations of European ancestry. However, it is under-studied whether other populations harbor different sets of hot-spot somatic mutations in these pathways and other oncogenes. In this study, to evaluate the mutational spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes, including genes in the four candidate pathways, as well as several known oncogenes for other cancers. Candidate mutations were validated by Sanger sequencing, and we further used SIFT and PolyPhen-2 to assess potentially functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases. Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7, BRAF and PTEN in Chinese CRC patients. While most were previously reported in CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our study confirmed the existence of known somatic mutations in the four candidate pathways for CRC in Chinese patients. We also discovered a number of novel somatic mutations in these pathways, which may have implications for the pathogenesis of CRC.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, United States of America; Laboratory of Clinical Genetics, Peking Union Medical College Hospital, Beijing, 100730, China; Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ling
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
authors.forename: Luming
authors.initials: L
authors.lastname: Xu
authors.affiliation: Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, United States of America; USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, United States of America; Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009857:Oncogenes / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011795:Surveys and Questionnaires; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D058118:Transcription Factor 7-Like 2 Protein; C555337:APC protein, human; C544894:TCF7L2 protein, human; C484760:PIK3CA protein, human