title: Heterogeneity of KRAS Mutations in Pancreatic Ductal Adenocarcinoma.
abstract: Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are the most common and frequent changes observed in pancreatic cancer. This study aimed to determine the frequency and extent of intratumoral and metastatic lymph node KRAS mutation heterogeneity of resected pancreatic ductal adenocarcinoma.
  
  
  
  Tumor tissues macrodissected from tumor centers, invasion fronts (n = 97), and lymph nodes (n = 11) were subjected to DNA extraction and mutation analysis of KRAS codons 12 and 13 by pyrosequencing.
  
  
  
  Activating mutations in codon 12 of KRAS were detected in 90 (92.8%) tumor centers. No mutations were detected in KRAS codon 13 in any patient. After a comparison of tumor centers and invasion fronts, intratumoral heterogeneity of KRAS was observed only in 4 (4.1%) cases. Additional invasion front tumor analysis revealed the same mutation status consistent with each tumor center. No heterogeneity was observed between primary tumors and metastatic lymph nodes.
  
  
  
  Intratumoral heterogeneity of the KRAS mutational status is rare in pancreatic ductal adenocarcinoma. In addition, no KRAS heterogeneity between primary tumors and metastatic lymph nodes was detected in this study. This finding is consistent with the hypothesis that oncogenic activation of KRAS is the first driver mutation in pancreatic cancer.
authors.affiliation: From the *Department of Gastroenterological Surgery and †Institute of Resource Development and Analysis, Kumamoto University Graduate School of Medical Sciences; and ‡Department of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Kota
authors.initials: K
authors.lastname: Arima
authors.forename: Naomi
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Akira
authors.initials: A
authors.lastname: Chikamoto
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Taki
authors.forename: Risa
authors.initials: R
authors.lastname: Inoue
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kaida
authors.forename: Takaaki
authors.initials: T
authors.lastname: Higashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nitta
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohmuraya
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirota
authors.forename: Toru
authors.initials: T
authors.lastname: Beppu
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D000230:Adenocarcinoma; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D004252:DNA Mutational Analysis; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)