title: Low frequency of KRAS mutation in pancreatic ductal adenocarcinomas in Korean patients and its prognostic value.
abstract: OBJECTIVE
  Low prevalence and prognostic relevance of KRAS mutations in Korean pancreatic ductal adenocarcinomas (PDACs) need to be validated with sensitive detection method.
  
  
  METHODS
  Peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping was used to precisely detect KRAS mutation in 72 paraffinized tumor samples and was validated by pancreatic cell lines to compare the efficiency of direct sequencing.
  
  
  RESULTS
  The PNA-mediated PCR clamping detected mutant allele proportions of as low as 0.5% against a background of wild-type DNA and was 20-fold more sensitive than direct sequencing through the validation of pancreatic cell lines. Peptide nucleic acid-mediated PCR clamping detected KRAS mutations in 47.2% of 72 PDACs. Low tumor cellularity and low PCR amplification efficiency led to be undetected or failed by direct sequencing in pancreatic paraffinized samples.KRAS mutations were an independent worse prognostic factor predicting a reduced progression-free survival rate in the postoperative chemotherapy group.
  
  
  CONCLUSIONS
  Peptide nucleic acid clamp real-time PCR was a sensitive method for detecting KRAS status in paraffinized PDAC samples. We identified a low KRAS mutation rate among the Korean PDAC patients using PNA clamp real-time PCR, potentially implicating epidemiological characteristics. The low KRAS mutation rate and its prognostic role may suggest the further survival benefit in Korean PDAC patients.
authors.affiliation: From the Departments of *Pathology and †Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang; Departments of ‡Pathology and §Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul; ‖Department of Hematological Oncology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang; and ¶Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, #Department of Pathology, Samsung Medical Center, Sungkyunkwan University College of Medicine, and **Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Jang Yong
authors.initials: JY
authors.lastname: Jeon
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Park
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Shin
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kwon
authors.forename: Joo Seop
authors.initials: JS
authors.lastname: Kim
authors.forename: Boram
authors.initials: B
authors.lastname: Han
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins