Monitoring KRAS mutations in circulating DNA and tumor cells using digital droplet PCR during treatment of KRAS-mutated lung adenocarcinoma.
Liquid biopsies are a new non-invasive strategy to detect and monitor the biology of non-small-cell lung cancer (NSCLC) in the era of personalized medicine. KRAS is an oncogenic driver that is mutated in 30% of NSCLCs and is associated with a poor prognosis. 62 samples from 32 patients, treated for metastatic KRAS-mutated lung adenocarcinoma, had DNA extracted from plasma and circulating tumor cells (CTCs) prospectively tested for the presence of KRAS mutations using droplet digital PCR. A KRAS mutation was detected in 82% of patients. Sensitivity was 78% for circulating free DNA (cfDNA) and 34% for CTCs. The presence of a KRAS mutation in cfDNA was correlated with a poor response to chemotherapy or targeted therapy. When a KRAS-mutated-DNA was detected and then monitored in cfDNA, its variation during targeted or conventional therapy was correlated with response, according to RECIST criteria, in 87.5% of cases (n=14/16), whereas this correlation was observed in 37.5% of cases for CTCs (n=3/8). We report the usefulness of using digital droplet PCR on liquid biopsies to predict and monitor responses to treatment of KRAS-mutated lung adenocarcinoma. ctDNA was much more sensitive than CTCs in this context.
Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France; Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France. Electronic address: nicolas.guibert@hotmail.fr.
Nicolas
N
Guibert
Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Institut Claudius Regaud, IUCT-Oncopole, Laboratoire de Biologie Médicale Oncologique, Toulouse, France.
Anne
A
Pradines
Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Institut Claudius Regaud, IUCT-Oncopole, Laboratoire de Biologie Médicale Oncologique, Toulouse, France.
Magali
M
Farella
Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Institut Claudius Regaud, IUCT-Oncopole, Laboratoire de Biologie Médicale Oncologique, Toulouse, France.
Anne
A
Casanova
Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France.
Sandrine
S
Gouin
Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Institut Claudius Regaud, IUCT-Oncopole, Laboratoire de Biologie Médicale Oncologique, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France.
Laura
L
Keller
Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; Institut Claudius Regaud, IUCT-Oncopole, Laboratoire de Biologie Médicale Oncologique, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France.
Gilles
G
Favre
Thoracic Oncology Department, Larrey Hospital, University Hospital of Toulouse, France; Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France; University of Toulouse III (Paul Sabatier), Toulouse, France. Electronic address: mazieres.j@chu-toulouse.fr.
Julien
J
Mazieres
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D016896:Treatment Outcome
D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
Circulating tumor DNA; Circulating tumor cells; KRAS mutation; Monitoring of response; Non-small-cell lung cancer