title: Mutation Spectra of Common Cancer-Associated Genes in Different Phenotypes of Colorectal Carcinoma Without Distant Metastasis.
abstract: BACKGROUND
  Colorectal cancer (CRC) is a heterogeneous disease caused by genetic and epigenetic alterations. This study aimed to describe the mutation frequency of 12 genes in different CRC phenotypes.
  
  
  METHODS
  Patients who underwent surgery at the Taipei Veterans General Hospital during 2000-2010 for CRC (n = 1249) were enrolled. The endpoint was overall survival. The prognostic value was determined with the log-rank test and Cox regression analysis.
  
  
  RESULTS
  We found 1836 mutations of 12 genes in 997 (79.8%) tumors. Mutations were most frequently in KRAS (485, 38.8%), TP53 (373, 29.9%), APC (363, 29.0%), and PIK3CA (179, 14.3%); 137 (11.0%) cancers had high microsatellite instability (MSI). Women had significantly higher high MSI (14.3%) and BRAF mutation (6.3%) frequencies. The abnormal MSI (21.7%) and KRAS (44.6%), BRAF (8.6%), PIK3CA (19.4%), AKT1 (2.2%), and TGF - βR (9.6%) mutation frequencies were significantly higher in proximal colon cancer. The high MSI (35.6%) and BRAF (20.3%), TGF - βR (18.6%), PTEN (5.1%), and AKT1 (3.4%) mutation frequencies were significantly higher in 59 (4.7%) poorly differentiated tumors. The high MSI (21.3%) and KRAS (51.9%), BRAF (8.3%), PIK3CA (25.0%), AKT1 (4.6%), and SMAD4 (8.3%) mutation frequencies were significantly higher in 108 mucinous tumors. TNM stage, lymphovascular invasion, and mucinous histology were significantly associated with patient outcomes in univariate and multivariate analyses. Only NRAS mutation (hazard ratio 1.59, 95% confidence interval 1.06-2.38) affected patient survival.
  
  
  CONCLUSIONS
  Mutational spectra differ significantly between CRC subtypes, implying diverse carcinogenetic pathways. The NRAS mutation is important, despite its low frequency.
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Clinical Pathology, Yang-Ming Campus, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Lin
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.affiliation: Division of Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Liang
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Shone
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. jkjiang@vghtpe.gov.tw.|Department of Surgery, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. jkjiang@vghtpe.gov.tw.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins