title: Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer.
abstract: OBJECTIVE
  Although the mutation status ofKRASis highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes.
  
  
  METHODS
  In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients' demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review.
  
  
  RESULTS
  In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency:KRAS(39.1%),TP53(28.3%),APC(28.3%),PIK3CA(6.5%),BRAF(6.5%), andNRAS(4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap.
  
  
  CONCLUSIONS
  These findings indicate the major pathway genes, includingKRAS,TP53,APC,PIK3CA,BRAF, andNRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.
authors.affiliation: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyu-Pyo
authors.initials: KP
authors.lastname: Kim
authors.affiliation: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.affiliation: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Chun
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.affiliation: Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
authors.affiliation: Division of Oncology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018631:ras Proteins
keywords: Colorectal neoplasms; Genomics; Neoplasm metastasis