Research outcomes

A novel technology to detect lung cancer mutations using next-generation sequencing of plasma DNA

The strong effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs; i.e., gefitinib and erlotinib) on non-small-cell lung cancer (NSCLC) are correlated with activating mutations in EGFR. Patients who are administered these drugs are selected based on the presence of these activating mutations. However, acquisition of cancer tissues, i.e., biopsy is invasive to patients, and non-invasive procedures, such as use of blood samples, have been long studied.

Cell-free DNA in the blood of cancer patients contains circulating tumor DNA (ctDNA), DNA derived from cancer tissues. Because ctDNA is rare, its detection is a technical challenge. Prof. Kikuya Kato and colleagues in Osaka International Cancer Institute developed a new technology to detect EGFR mutations in plasma DNA from lung cancer patients. This technology enables detection of rare mutations using next-generation sequencing of more than 50,000 molecules. Premarket application of the technology was submitted to Ministry of Health, Labor and Welfare by DNA Chip Research Inc. on July 10, 2019.

Comments by Prof. Kato

The technology described above was published in 2013. However, the scientific assessment of medical technologies does not complete until the approval by the Ministry of Health, Labor and Welfare. We performed substantial clinical studies and various analytical experiments until this application. Although the application marks a major milestone of our project, we will continue research and development for wide spread use of the technology.


Kukita, Y., Uchida, J., Oba, S., Nishino, K., Kumagai, T., Tanguchi, K., Okukyma, T., Imamura, F. and Kato, K. Quantitative identification of mutant alleles derived from lung cancer in plasma cell-free DNA via anomaly detection using deep sequencing data, PLoS ONE 8 (2013): e81468.

Uchida, J., Kato, K., Kukita, Y., Kumagai, T., Nishino, K., Daga, H., Nagatomo, I., Inoue, T., Kimura, M., Oba, S., Ito, Y., Takeda, K. and Imamura, F. Diagnostic accuracy of noninvasive genotyping of EGFR in lung cancer patients using deep sequencing of plasma cell-free DNA. Clinical Chemistry, 51 (2015) 1191–1196.

【Medical Genomics Laboratory】

[ Press Release ] July 10, 2019

( August 01, 2019 )