TY - JOUR
T1 - Utility of assessing the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes using a targeted deep sequencing assay as a prognostic biomarker for pancreatic cancer
AU - Hayashi, Hideyuki
AU - Kohno, Takashi
AU - Ueno, Hideki
AU - Hiraoka, Nobuyoshi
AU - Kondo, Shunsuke
AU - Saito, Motonobu
AU - Shimada, Yoko
AU - Ichikawa, Hitoshi
AU - Kato, Mamoru
AU - Shibata, Tatsuhiro
AU - Morizane, Chigusa
AU - Sakamoto, Yasunari
AU - Shimada, Kazuaki
AU - Komatsu, Yoshito
AU - Sakamoto, Naoya
AU - Okusaka, Takuji
N1 - Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Objectives: KRAS, CDKN2A, TP53, and SMAD4 have been recognized as major driver genes in pancreatic carcinogenesis. We examined somatic mutations in 50 cancer-related genes, including the four above-mentioned driver genes, to identify genomic biomarkers for predicting the outcome of patients with pancreatic cancer. Methods: Genomic DNA was extracted from fresh-frozen specimens obtained from 100 patients with pancreatic cancer who had undergone a pancreatectomy with curative intent. The mutation profile was obtained using a single targeted deep sequencing assay performed with a nextgeneration sequencer, and the associations with clinicopathological factors were analyzed. Results: Mutations in the KRAS, CDKN2A, TP53, and SMAD4 genes were detected in 96% (96/100), 42% (42/100), 13% (13/100), and 7% (7/100) of all patients, respectively. Among the 71 patients who underwent a radical operation followed by adjuvant chemotherapy, patients with fewer mutations among the four driver genes tended to have a better outcome. A multivariate analysis using the Cox proportional hazard model showed that the presence of 0 to 2 mutated driver genes was an independent predictor of a better overall survival (hazard ratio for death, 0.20; P = 0.0040). Conclusions: The number of mutated driver genes assessed using a targeted deep sequencing assay was a promising prognostic biomarker for pancreatic cancer.
AB - Objectives: KRAS, CDKN2A, TP53, and SMAD4 have been recognized as major driver genes in pancreatic carcinogenesis. We examined somatic mutations in 50 cancer-related genes, including the four above-mentioned driver genes, to identify genomic biomarkers for predicting the outcome of patients with pancreatic cancer. Methods: Genomic DNA was extracted from fresh-frozen specimens obtained from 100 patients with pancreatic cancer who had undergone a pancreatectomy with curative intent. The mutation profile was obtained using a single targeted deep sequencing assay performed with a nextgeneration sequencer, and the associations with clinicopathological factors were analyzed. Results: Mutations in the KRAS, CDKN2A, TP53, and SMAD4 genes were detected in 96% (96/100), 42% (42/100), 13% (13/100), and 7% (7/100) of all patients, respectively. Among the 71 patients who underwent a radical operation followed by adjuvant chemotherapy, patients with fewer mutations among the four driver genes tended to have a better outcome. A multivariate analysis using the Cox proportional hazard model showed that the presence of 0 to 2 mutated driver genes was an independent predictor of a better overall survival (hazard ratio for death, 0.20; P = 0.0040). Conclusions: The number of mutated driver genes assessed using a targeted deep sequencing assay was a promising prognostic biomarker for pancreatic cancer.
KW - Clinical sequencing
KW - Driver mutation
KW - Genomic biomarker
KW - Next-generation sequencer
KW - Precision medicine
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U2 - 10.1097/MPA.0000000000000760
DO - 10.1097/MPA.0000000000000760
M3 - Article
C2 - 28099251
AN - SCOPUS:85009737831
VL - 46
SP - 335
EP - 340
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 3
ER -