Acquired/intratumoral mutation of KRAS during metastatic progression of colorectal carcinogenesis

Otsuka,Kazunori; Satoyoshi,Rika; Nanjo,Hiroshi; Miyazawa,Hideaki; Abe,Yuki; Tanaka,Masamitsu; Yamamoto,Yuzo; Shibata,Hiroyuki

doi:10.3892/ol.2011.543

March 2012 Volume 3 Issue 3

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March 2012 Volume 3 Issue 3

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Article

Acquired/intratumoral mutation of KRAS during metastatic progression of colorectal carcinogenesis

Authors:
- Kazunori Otsuka
- Rika Satoyoshi
- Hiroshi Nanjo
- Hideaki Miyazawa
- Yuki Abe
- Masamitsu Tanaka
- Yuzo Yamamoto
- Hiroyuki Shibata
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Affiliations: Department of Clinical Oncology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan, Department of Molecular Medicine and Biochemistry, Graduate School of Medicine, Akita University, Akita 010-8543, Japan, Department of Pathology, Graduate School of Medicine, Akita University, Akita 010-8543, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Akita University, Akita 010-8543, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Akita University, Akita 010-8543, Japan
Pages: 649-653
|
Published online on: December 29, 2011

https://doi.org/10.3892/ol.2011.543
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Abstract

Mutations at codons 12 and 13 of the KRAS gene have been identified as level I predictive biomarkers against the treatment of advanced colorectal cancer with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. It is thought that the genetic analysis of KRAS mutations associated with metastatic colorectal cancer can be routinely conducted using DNA obtained on one occasion from one organ, from the primary or a metastatic site, whichever is preferentially available. However, the issue of tumor heterogeneity resulting from acquired/intratumoral mutations remains. Recently, the possibility of acquired/intratumoral mutations in the KRAS gene has been reported by two research groups and has ranged from 7.4 to 15.4%. Specimens were collected from advanced colorectal cancer patients with resected primary, and at least one metastatic, site. Direct sequence analysis was performed for KRAS, BRAF and PIK3CA, and immunohistochemistry for glutathione S-transferase II (GSTP) and EGFR. In the current study, we identified an acquired mutation rate of approximately 11.1% in the KRAS gene (1/9). This figure is not negligible. Our observation indicates, particularly in the case of metastatic recurrence after a long interval, that there may be considerable tumor heterogeneity resulting from acquired or intratumoral mutations of the KRAS gene.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Acquired/intratumoral mutation of KRAS during metastatic progression of colorectal carcinogenesis

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Abstract

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