Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer

Hideaki Kunugasa, Kazuhiro Nouso, Koji Miyahara, Yuki Morimoto, Chihiro Dohi, Koichiro Tsutsumi, Hironari Katou, Takehiro Matsubara, Hiroyuki Okada, Kazuhide Yamamoto

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. Cancer 2015;121:2271-2280.

Original languageEnglish
Pages (from-to)2271-2280
Number of pages10
JournalCancer
Volume121
Issue number13
DOIs
Publication statusPublished - Jul 1 2015

Fingerprint

ras Genes
Pancreatic Neoplasms
Biopsy
Mutation
DNA
Neoplasms
Mutation Rate
Endoscopic Ultrasound-Guided Fine Needle Aspiration
Circulating Neoplastic Cells
Tissue Survival
Survival
DNA-Directed DNA Polymerase
Fine Needle Biopsy
Serum
Codon
Survival Rate
Polymerase Chain Reaction

Keywords

  • circulating DNA
  • circulating tumor DNA (ctDNA)
  • digital polymerase chain reaction
  • K-ras
  • liquid biopsy
  • pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kunugasa, H., Nouso, K., Miyahara, K., Morimoto, Y., Dohi, C., Tsutsumi, K., ... Yamamoto, K. (2015). Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. Cancer, 121(13), 2271-2280. https://doi.org/10.1002/cncr.29364

Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. / Kunugasa, Hideaki; Nouso, Kazuhiro; Miyahara, Koji; Morimoto, Yuki; Dohi, Chihiro; Tsutsumi, Koichiro; Katou, Hironari; Matsubara, Takehiro; Okada, Hiroyuki; Yamamoto, Kazuhide.

In: Cancer, Vol. 121, No. 13, 01.07.2015, p. 2271-2280.

Research output: Contribution to journalArticle

Kunugasa, H, Nouso, K, Miyahara, K, Morimoto, Y, Dohi, C, Tsutsumi, K, Katou, H, Matsubara, T, Okada, H & Yamamoto, K 2015, 'Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer', Cancer, vol. 121, no. 13, pp. 2271-2280. https://doi.org/10.1002/cncr.29364
Kunugasa H, Nouso K, Miyahara K, Morimoto Y, Dohi C, Tsutsumi K et al. Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. Cancer. 2015 Jul 1;121(13):2271-2280. https://doi.org/10.1002/cncr.29364
Kunugasa, Hideaki ; Nouso, Kazuhiro ; Miyahara, Koji ; Morimoto, Yuki ; Dohi, Chihiro ; Tsutsumi, Koichiro ; Katou, Hironari ; Matsubara, Takehiro ; Okada, Hiroyuki ; Yamamoto, Kazuhide. / Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer. In: Cancer. 2015 ; Vol. 121, No. 13. pp. 2271-2280.
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abstract = "BACKGROUND Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3{\%}), 22 of 75 samples (29.3{\%}), and 6 of 75 samples (8.0{\%}), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6{\%}), 29 of 75 samples (38.6{\%}), and 4 of 75 samples (5.3{\%}), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7{\%} and 62.6{\%}, respectively, and the concordance rate between them was 58 of 75 samples (77.3{\%}). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. Cancer 2015;121:2271-2280.",
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AU - Kunugasa, Hideaki

AU - Nouso, Kazuhiro

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AU - Morimoto, Yuki

AU - Dohi, Chihiro

AU - Tsutsumi, Koichiro

AU - Katou, Hironari

AU - Matsubara, Takehiro

AU - Okada, Hiroyuki

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N2 - BACKGROUND Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. Cancer 2015;121:2271-2280.

AB - BACKGROUND Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival. Cancer 2015;121:2271-2280.

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