BACKGROUND: A gatekeeper T790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI. METHODS: We used a competitive allele-specific polymerase chain reaction (CAST-PCR) to analyze the incidence and clinical significance of T790M mutations in 153 lung adenocarcinomas with EGFR-activating mutations. To increase the sensitivity and specificity of the detection of T790M mutations, we subjected 20 of the 153 cases to a digital PCR. The genomic DNAs were extracted from frozen, surgically resected tumor tissue specimens. RESULTS: The CAST-PCR detected T790M mutations in 45 (29.4%) of the 153 cases. The analytical sensitivity in the detection T790M mutations was 0.13-2.65% (average 0.27%, median 0.20%). In contrast, the digital PCR, detected T790M mutations in 8 (40%) out of 20 cases. CONCLUSIONS: Our study shows that the pretreatment incidence of T790M mutation was less than that reported in previous studies. In order to clinically use pretreatment EGFR T790M mutation identification method, we should clarify the adequate methods and tissue preserved status.
BACKGROUND: A gatekeeperT790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI. METHODS: We used a competitive allele-specific polymerase chain reaction (CAST-PCR) to analyze the incidence and clinical significance of T790M mutations in 153 lung adenocarcinomas with EGFR-activating mutations. To increase the sensitivity and specificity of the detection of T790M mutations, we subjected 20 of the 153 cases to a digital PCR. The genomic DNAs were extracted from frozen, surgically resected tumor tissue specimens. RESULTS: The CAST-PCR detected T790M mutations in 45 (29.4%) of the 153 cases. The analytical sensitivity in the detection T790M mutations was 0.13-2.65% (average 0.27%, median 0.20%). In contrast, the digital PCR, detected T790M mutations in 8 (40%) out of 20 cases. CONCLUSIONS: Our study shows that the pretreatment incidence of T790M mutation was less than that reported in previous studies. In order to clinically use pretreatment EGFRT790M mutation identification method, we should clarify the adequate methods and tissue preserved status.
Entities:
Keywords:
CAST-PCR; EGFR mutation; Non-small cell lung cancer (NSCLC); T790M mutation; digital PCR
Authors: Rafael Rosell; Miguel Angel Molina; Carlota Costa; Sara Simonetti; Ana Gimenez-Capitan; Jordi Bertran-Alamillo; Clara Mayo; Teresa Moran; Pedro Mendez; Felipe Cardenal; Dolores Isla; Mariano Provencio; Manuel Cobo; Amelia Insa; Rosario Garcia-Campelo; Noemi Reguart; Margarita Majem; Santiago Viteri; Enric Carcereny; Ruth Porta; Bartomeu Massuti; Cristina Queralt; Itziar de Aguirre; Jose Miguel Sanchez; Maria Sanchez-Ronco; Jose Luis Mate; Aurelio Ariza; Susana Benlloch; Jose Javier Sanchez; Trever G Bivona; Charles L Sawyers; Miquel Taron Journal: Clin Cancer Res Date: 2011-01-13 Impact factor: 12.531