689P - Gene mutation profile of pancreatic cancer obtained using targeted deep sequencing and its association with prognosis

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Pancreatic Cancer
Translational Research
Presenter Hideyuki Hayashi
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors H. Hayashi1, T. Kohno2, N. Hiraoka3, Y. Sakamoto1, S. Kondo1, C. Morizane1, M. Saito2, K. Shimada4, H. Ichikawa5, Y. Komatsu6, H. Ueno1, T. Okusaka1
  • 1Department Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Division Of Genome Biology, National Cancer Center Research Institute, Tokyo/JP
  • 3Division Of Molecular Pathology, National Cancer Center Research Institute, Tokyo/JP
  • 45) department Of Hepatobiliary And Pancreatic Surgery, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5Division Of Genetics, National Cancer Center Research Institute, Tokyo/JP
  • 6Cancer Center, Hokkaido University, 060-8638 - Sapporo/JP



Activating KRAS mutations are the major driver gene aberrations of pancreatic cancer and are present in over 90% of patients with pancreatic cancer. On the other hand, aberrations of the CDKN2A, TP53, and SMAD4 genes are also frequent events in pancreatic carcinogenesis. We constructed a mutation profile of pancreatic cancer-associated genes. Additionally, we analyzed the relationship between gene mutations and clinicopathological factors.


Genomic DNA samples were extracted from fresh frozen surgical specimens obtained from 100 patients (98 with pancreatic ductal adenocarcinoma, 2 with adenosquamous carcinoma) who underwent radical operations for pancreatic cancer at the National Cancer Center Hospital between March 2005 and June 2012. Next-generation sequencer-based targeted deep sequencing was performed using a Cancer Panel reagent that covers representative cancer-related genes (50 genes, 190 hot spots).


Mutations were detected in 97% of the cases, and the average number of mutations per tumor sample was 1.6. The most frequently mutated genes were KRAS (96%), TP53 (42%), SMAD4 (13%), and CDKN2A (7%). The most common mutation types of KRAS were G12D (48%), G12V (32%), and G12R (10%) in our cohort. The known druggable mutations that were detected were GNAS (1%), PIK3CA (1%), and KIT (1%). Among the patients who underwent radical operations followed by adjuvant chemotherapy (71 patients), the survival of patients who had 0 to 2 mutations in the 4 major driver genes (KRAS, TP53, SMAD4, and CDKN2A) was significantly longer than that of patients who had 3 or more mutations (median overall survival, 40.0 months vs. 12.6 months, P = 0.0020). A multivariate Cox proportional hazard model analysis showed that a low number of mutations among these 4 genes was significantly associated with a better prognosis.


KRAS, TP53, SMAD4, and CDKN2A were the most frequently mutated genes in Japanese patients with pancreatic cancer. The number of mutations among these 4 genes as detected using targeted deep sequencing may be a useful biomarker for the prediction of postoperative outcomes.


All authors have declared no conflicts of interest.