title: KRAS, BRAF, and PIK3CA mutations, and patient prognosis in 126 pancreatic cancers: pyrosequencing technology and literature review.
abstract: The oncogenic hallmarks of pancreatic cancer (PC), such as the KRAS, BRAF, and PIK3CA mutations, have been widely investigated. However, almost all of the previous studies were limited by small sample sizes. In addition, previous data on the KRAS mutation and clinical outcomes in PC remain inconclusive. To clarify these data, we examined the mutation status of 126 PC patients and its relationship to clinical outcome. The frequencies of KRAS, BRAF, and PIK3CA mutations were determined from a non-biased database of 126 resected PCs and a high-throughput pyrosequencing assay. KRAS mutations were detected in 109 (86.5 %) of the 126 cases; the most common mutation was c.34G > T (p.G12C), which was present in 80 tumors, followed by c.35G > T (p.G12V) in 52 tumors. The KRAS mutation was not associated with any clinical or pathological features (p > 0.05 in all cases). In addition, the KRAS mutation was unrelated to overall survival (log rank p = 0.21) and cancer-specific survival (log rank p = 0.27). Importantly, the influence of KRAS mutation on patient outcome was not modified by any of the clinical or pathological variables (p for all interactions >0.05). Only one PIK3CA mutation (0.8 %) was detected on exon 9 RS3 (c.1633G > A, p.E545K). The BRAF mutation was not detected in PC. KRAS mutations appear to be unrelated to clinical outcome in PC. BRAF and PIK3CA mutations were extremely rare in PC, suggesting that they play a limited role in PC development.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.|Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kitano
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Yamamura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosumi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kaida
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Arima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Taki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Chikamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Beppu
authors.affiliation: Department of Pancreatic and Thyroidal Surgery, China Medical University Shengjing Hospital, Shenyang, 110004, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. hdobaba@kumamoto-u.ac.jp.
authors.forename: Hideo
authors.identifier: http://orcid.org/0000-0003-3963-8653
authors.initials: H
authors.lastname: Baba
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; KRAS; Mutation; PIK3CA; Pancreatic cancer