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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2013

Open Access 01-12-2013 | Translational Research and Biomarkers

KRAS and BRAF Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Authors: Hironobu Shigaki, MD, Yoshifumi Baba, MD, PhD, Masayuki Watanabe, MD, PhD, FACS, Keisuke Miyake, MSc, Asuka Murata, MD, Shiro Iwagami, MD, PhD, Takatsugu Ishimoto, MD, PhD, Masaaki Iwatsuki, MD, PhD, Naoya Yoshida, MD, PhD, Hideo Baba, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Special Issue 3/2013

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Abstract

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.
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Metadata
Title
KRAS and BRAF Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review
Authors
Hironobu Shigaki, MD
Yoshifumi Baba, MD, PhD
Masayuki Watanabe, MD, PhD, FACS
Keisuke Miyake, MSc
Asuka Murata, MD
Shiro Iwagami, MD, PhD
Takatsugu Ishimoto, MD, PhD
Masaaki Iwatsuki, MD, PhD
Naoya Yoshida, MD, PhD
Hideo Baba, MD, PhD, FACS
Publication date
01-12-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2819-z

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