Low frequency of KRAS mutation in pancreatic ductal adenocarcinomas in Korean patients and its prognostic value

• Published in: Pancreas Vol. 44; no. 3; p. 484
• Main Authors: Kwon, Mi Jung, Jeon, Jang Yong, Park, Hye-Rim, Nam, Eun Sook, Cho, Seong Jin, Shin, Hyung Sik, Kwon, Ji Hyun, Kim, Joo Seop, Han, Boram, Kim, Dong Hoon, Choi, Yoon-La
• Format: Journal Article
• Language: English
• Published: United States 01.04.2015
• Subjects: Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; Biomarkers, Tumor - genetics; Carcinoma, Pancreatic Ductal - ethnology; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; Cell Line, Tumor; Disease-Free Survival; DNA Mutational Analysis - methods; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Pancreatic Neoplasms - ethnology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Phenotype; Predictive Value of Tests; Proportional Hazards Models; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Republic of Korea - epidemiology; Risk Factors; Time Factors; Treatment Outcome
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0000000000000280

Low prevalence and prognostic relevance of KRAS mutations in Korean pancreatic ductal adenocarcinomas (PDACs) need to be validated with sensitive detection method. 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. 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. 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.