title: Usefulness of nanofluidic digital PCR arrays to quantify T790M mutation in EGFR-mutant lung adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Isobe
authors.affiliation: Division Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Naobumi
authors.initials: N
authors.lastname: Tochigi
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Kaburaki
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Division Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Makino
authors.affiliation: Division Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ishida
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Hirota
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Sano
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugino
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Takai
authors.affiliation: Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Division Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.affiliation: Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Homma
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D010865:Pilot Projects; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies
chemical_list: D066246:ErbB Receptors
keywords: Digital PCR; T790M; epidermal growth factor receptor tyrosine kinase inhibitor; non-small-cell lung cancer