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Case Report Open Access

Amplification of mutant KRASG12D in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report

  • Authors:
    • Fabio Pittella‑Silva
    • Yasutoshi Kimura
    • Siew-Kee Low
    • Yusuke Nakamura
    • Masayo Motoya
  • View Affiliations / Copyright

    Affiliations: Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo 135‑8550, Japan, Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo 060‑8543, Japan, Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060‑8543, Japan
    Copyright: © Pittella‑Silva et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 172
    |
    Published online on: June 29, 2021
       https://doi.org/10.3892/mco.2021.2334
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancer types. Activating oncogenic KRAS mutations are commonly observed in PDAC; however, oncogenic KRAS amplification is rarely observed, and its significance in prognosis and resistance to therapy remains poorly characterized. The present report describes the case of a 52‑year‑old male patient diagnosed with advanced PDAC with liver metastasis. The patient received modified FOLFIRINOX (mFFX) therapy to which the patient became intolerant with a strong inflammatory response. Subsequent treatment with gemcitabine plus nab‑paclitaxel failed to control the disease. Targeted genetic analysis revealed KRASG12D and TP53R248Q mutations in the primary tumor and liver metastases. Analysis of circulating tumor DNA (ctDNA) before the first line of treatment confirmed these genetic findings and revealed a >4‑fold amplification of the mutant KRASG12D not detected in the primary tumor. Additionally, subsequent analysis confirmed a 5‑fold amplification of the KRASG12D allele in liver metastasis. Consecutive monitoring of ctDNA revealed an initial decrease in the tumor burden 2 weeks after the first cycle of mFFX. However, coinciding with treatment intolerance, a sharp increase in tumor mutational levels and KRASG12D amplification was observed 1 month later. The patient died 70 days after treatment initiation. Overall, amplification of oncogenic KRASG12D was not only associated with an aggressive phenotype, but also supported cancer resistance to chemotherapy. Importantly, this case suggests that plasma detection of KRASG12D amplification is feasible in the clinical routine and constitutes a powerful tool for assessing tumor aggressiveness.
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Copy and paste a formatted citation
Spandidos Publications style
Pittella‑Silva F, Kimura Y, Low S, Nakamura Y and Motoya M: Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report. Mol Clin Oncol 15: 172, 2021.
APA
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., & Motoya, M. (2021). Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report. Molecular and Clinical Oncology, 15, 172. https://doi.org/10.3892/mco.2021.2334
MLA
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., Motoya, M."Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report". Molecular and Clinical Oncology 15.3 (2021): 172.
Chicago
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., Motoya, M."Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report". Molecular and Clinical Oncology 15, no. 3 (2021): 172. https://doi.org/10.3892/mco.2021.2334
Copy and paste a formatted citation
x
Spandidos Publications style
Pittella‑Silva F, Kimura Y, Low S, Nakamura Y and Motoya M: Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report. Mol Clin Oncol 15: 172, 2021.
APA
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., & Motoya, M. (2021). Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report. Molecular and Clinical Oncology, 15, 172. https://doi.org/10.3892/mco.2021.2334
MLA
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., Motoya, M."Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report". Molecular and Clinical Oncology 15.3 (2021): 172.
Chicago
Pittella‑Silva, F., Kimura, Y., Low, S., Nakamura, Y., Motoya, M."Amplification of mutant <em>KRAS</em><sup>G12D</sup> in a patient with advanced metastatic pancreatic adenocarcinoma detected by liquid biopsy: A case report". Molecular and Clinical Oncology 15, no. 3 (2021): 172. https://doi.org/10.3892/mco.2021.2334
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