Usefulness of Nanofluidic Digital PCR Arrays to Quantify T790M Mutation in EGFR-mutant Lung Adenocarcinoma

作者：Isobe Kazutoshi^*; Hata Yoshinobu; Tochigi Naobumi; Kaburaki Kyohei; Kobayashi Hiroshi; Makino Takashi; Otsuka Hajime; Ishida Fumiaki; Hirota Nao; Sano Go; Sugino Keishi; Sakamoto Susumu; Takai Yujiro; Shibuya Kazutoshi; Iyoda Akira; Homma Sakae

来源：Cancer Genomics and Proteomics, 2015, 12(1): 31-37.

• Digital PCR
• non-small-cell lung cancer
• epidermal growth factor receptor tyrosine kinase inhibitor
• T790M

Aim: The present pilot study assessed the usefulness of nanofluidic digital polymerase chain reaction (PCR) arrays in epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma after tyrosine kinase inhibitor (TKI) resistance. Patients and Methods: We enrolled 12 patients with primary lung adenocarcinoma with sensitive EGFR mutation-confirmed T790M status by re-biopsy after TKI resistance. Nanofluidic digital PCR arrays were used to quantify T790M in genomic DNA from the pre-treatment primary site and in serum cell-free DNA (cfDNA). Results: On digital PCR, quantified T790M at the pre-treatment primary site was higher in re-biopsy-positive T790M patients (n=4) than in re-biopsy-negative patients (n=8) (0.78% +/- 0.36% vs. 0.07%+/- 0.09%, p< 0.01). T790M at the pre-treatment primary site correlated with progression-free survival (PFS) after gefitinib therapy (r=0.67, p=0.016). Conclusion: Use of digital PCR to quantify T790M at the primary site of EGFR-mutant lung adenocarcinoma predicted T790M emergence in re-biopsies after TKI resistance and PFS after gefitinib therapy.

• 出版日期2015-2