BACKGROUND: The epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, tissues for the genotyping of the EGFR T790M mutation can be difficult to obtain in a clinical setting. The aims of this study were to evaluate a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients using the PointMan™ EGFR DNA enrichment kit, which is a novel method for the selective amplification of specific genotype sequences. METHODS: Blood samples were collected from NSCLC patients who had activating EGFR mutations and who were resistant to EGFR-TKI treatment. Using cell-free DNA (cfDNA) from plasma, EGFR T790M mutations were amplified using the PointMan™ enrichment kit, and all the reaction products were confirmed using direct sequencing. The concentrations of plasma DNA were then determined using quantitative real-time PCR. RESULTS: Nineteen patients were enrolled, and 12 patients (63.2%) were found to contain EGFR T790M mutations in their cfDNA, as detected by the kit. T790M mutations were detected in tumor tissues in 12 cases, and 11 of these cases (91.7%) also exhibited the T790M mutation in cfDNA samples. The concentrations of cfDNA were similar between patients with the T790M mutation and those without the mutation. CONCLUSIONS: The PointMan™ kit provides a useful method for determining the EGFR T790M mutation status in cfDNA.
BACKGROUND: The epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, tissues for the genotyping of the EGFR T790M mutation can be difficult to obtain in a clinical setting. The aims of this study were to evaluate a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients using the PointMan™ EGFR DNA enrichment kit, which is a novel method for the selective amplification of specific genotype sequences. METHODS: Blood samples were collected from NSCLC patients who had activating EGFR mutations and who were resistant to EGFR-TKI treatment. Using cell-free DNA (cfDNA) from plasma, EGFR T790M mutations were amplified using the PointMan™ enrichment kit, and all the reaction products were confirmed using direct sequencing. The concentrations of plasma DNA were then determined using quantitative real-time PCR. RESULTS: Nineteen patients were enrolled, and 12 patients (63.2%) were found to contain EGFR T790M mutations in their cfDNA, as detected by the kit. T790M mutations were detected in tumor tissues in 12 cases, and 11 of these cases (91.7%) also exhibited the T790M mutation in cfDNA samples. The concentrations of cfDNA were similar between patients with the T790M mutation and those without the mutation. CONCLUSIONS: The PointMan™ kit provides a useful method for determining the EGFR T790M mutation status in cfDNA.
Entities:
Keywords:
Cell-free DNA (cfDNA); T790M; epidermal growth factor receptor (EGFR); lung cancer
Authors: Rafael Rosell; Enric Carcereny; Radj Gervais; Alain Vergnenegre; Bartomeu Massuti; Enriqueta Felip; Ramon Palmero; Ramon Garcia-Gomez; Cinta Pallares; Jose Miguel Sanchez; Rut Porta; Manuel Cobo; Pilar Garrido; Flavia Longo; Teresa Moran; Amelia Insa; Filippo De Marinis; Romain Corre; Isabel Bover; Alfonso Illiano; Eric Dansin; Javier de Castro; Michele Milella; Noemi Reguart; Giuseppe Altavilla; Ulpiano Jimenez; Mariano Provencio; Miguel Angel Moreno; Josefa Terrasa; Jose Muñoz-Langa; Javier Valdivia; Dolores Isla; Manuel Domine; Olivier Molinier; Julien Mazieres; Nathalie Baize; Rosario Garcia-Campelo; Gilles Robinet; Delvys Rodriguez-Abreu; Guillermo Lopez-Vivanco; Vittorio Gebbia; Lioba Ferrera-Delgado; Pierre Bombaron; Reyes Bernabe; Alessandra Bearz; Angel Artal; Enrico Cortesi; Christian Rolfo; Maria Sanchez-Ronco; Ana Drozdowskyj; Cristina Queralt; Itziar de Aguirre; Jose Luis Ramirez; Jose Javier Sanchez; Miguel Angel Molina; Miquel Taron; Luis Paz-Ares Journal: Lancet Oncol Date: 2012-01-26 Impact factor: 41.316
Authors: Lecia V Sequist; Jean-Charles Soria; Jonathan W Goldman; Heather A Wakelee; Shirish M Gadgeel; Andrea Varga; Vassiliki Papadimitrakopoulou; Benjamin J Solomon; Geoffrey R Oxnard; Rafal Dziadziuszko; Dara L Aisner; Robert C Doebele; Cathy Galasso; Edward B Garon; Rebecca S Heist; Jennifer Logan; Joel W Neal; Melody A Mendenhall; Suzanne Nichols; Zofia Piotrowska; Antoinette J Wozniak; Mitch Raponi; Chris A Karlovich; Sarah Jaw-Tsai; Jeffrey Isaacson; Darrin Despain; Shannon L Matheny; Lindsey Rolfe; Andrew R Allen; D Ross Camidge Journal: N Engl J Med Date: 2015-04-30 Impact factor: 91.245
Authors: Maria E Arcila; Geoffrey R Oxnard; Khedoudja Nafa; Gregory J Riely; Stephen B Solomon; Maureen F Zakowski; Mark G Kris; William Pao; Vincent A Miller; Marc Ladanyi Journal: Clin Cancer Res Date: 2011-01-19 Impact factor: 12.531
Authors: Lecia V Sequist; James Chih-Hsin Yang; Nobuyuki Yamamoto; Kenneth O'Byrne; Vera Hirsh; Tony Mok; Sarayut Lucien Geater; Sergey Orlov; Chun-Ming Tsai; Michael Boyer; Wu-Chou Su; Jaafar Bennouna; Terufumi Kato; Vera Gorbunova; Ki Hyeong Lee; Riyaz Shah; Dan Massey; Victoria Zazulina; Mehdi Shahidi; Martin Schuler Journal: J Clin Oncol Date: 2013-07-01 Impact factor: 44.544
Authors: Geoffrey R Oxnard; Kenneth S Thress; Ryan S Alden; Rachael Lawrance; Cloud P Paweletz; Mireille Cantarini; James Chih-Hsin Yang; J Carl Barrett; Pasi A Jänne Journal: J Clin Oncol Date: 2016-06-27 Impact factor: 44.544