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Updated: Jul 7, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
PIK3CA mutation status in Japanese esophageal squamous cell carcinoma
Ryota Mori1, Hideyuki Ishiguro, Masahiro Kimura
1Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.
Background:
A somatic mutation of the PIK3CA (phosphatidylinositol 3-kinase catalytic subunit) gene has been found in human cancer patients. However, this mutation has not yet been extensively studied in esophageal squamous cell carcinomas.
Materials And Methods:
We analyzed a mutation of the PIK3CA gene in 88 Japanese cases of esophageal squamous cell carcinomas that had all undergone surgery at the Department of Surgery II, Nagoya City University Medical School, between 1996 and 2003. The TE and KYSE series of cell lines are human esophageal cancer cell lines. Two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by a real time polymerase chain reaction (PCR)-based assay and the data were confirmed by direct sequencing. We performed a cell proliferation assay to determine the effects of a PI3K inhibitor LY294002.
Result:
In exon 9, a somatic mutation was found in two patients (2.2%) and in two cell lines. The mutations included three E545K (G1633A) mutations and one E545Q (G1633C) mutation. However, in exon 20, no mutation was observed in our esophageal cancer patients. PI3K inhibitor (LY294002) inhibited the growth of an esophageal cancer cell line with a PIK3CA mutation (E545K) in vitro.
Conclusions:
We found LY294002 to reduce the proliferation of the esophageal cancer cell line in vitro. Importantly, a cell line with a PIK3CA gene mutation was more susceptible to a PI3K inhibition than those without any such mutation. Further functional analyses of the PIK3CA mutations are warranted to determine whether or not they may be potentially useful targets of therapy for esophageal cancer.
Insights
Somatic PIK3CA gene mutations in esophageal cancer were investigated. A PI3K inhibitor reduced proliferation in cell lines with PIK3CA mutations, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in the PIK3CA gene are observed in various cancers.
- PIK3CA mutations are understudied in esophageal squamous cell carcinomas.
Purpose of the Study:
- To analyze PIK3CA gene mutations in esophageal squamous cell carcinomas.
- To investigate the effect of PI3K inhibition on esophageal cancer cell lines with PIK3CA mutations.
Main Methods:
- Analysis of PIK3CA mutations in 88 Japanese esophageal squamous cell carcinoma cases and cell lines.
- Real-time PCR and direct sequencing to detect mutations in PIK3CA exons 9 and 20.
- Cell proliferation assays using the PI3K inhibitor LY294002.
Main Results:
- Somatic PIK3CA mutations (E545K, E545Q) were identified in 2.2% of patients and in two cell lines.
- No PIK3CA mutations were detected in exon 20 of the patient cohort.
- The PI3K inhibitor LY294002 inhibited esophageal cancer cell growth in vitro, particularly in cell lines with PIK3CA mutations.
Conclusions:
- PIK3CA mutations in esophageal cancer cells increase susceptibility to PI3K inhibition.
- The PI3K inhibitor LY294002 demonstrates potential for treating esophageal cancer with PIK3CA mutations.
- Further research into PIK3CA mutations may reveal new therapeutic targets for esophageal cancer.
