+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Highly sensitive detection of EGFR T790M mutation using colony hybridization predicts favorable prognosis of patients with lung cancer harboring activating EGFR mutation



Highly sensitive detection of EGFR T790M mutation using colony hybridization predicts favorable prognosis of patients with lung cancer harboring activating EGFR mutation



Journal of Thoracic Oncology 7(11): 1640-1644



Approximately 50% of lung cancer patients with epidermal growth factor receptor (EGFR)-mutations (deletion in exon 19 or L858R) who develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) reportedly carry a secondary EGFR T790M mutation. This mutation has been suggested to be present in tumor cells before EGFR-TKI treatment in a small population of individuals. Here, we use a highly sensitive colony hybridization technique in an attempt to evaluate the actual incidence of T790M in pretreatment tumor specimens. DNA was extracted from surgically resected tumor tissues of 38 patients with the EGFR mutation and examined for the presence of T790M, using a standard polymerase chain reaction based method followed by a modified colony hybridization (CH) technique with an analytical sensitivity of approximately 0.01%. Associations between the T790M status and clinical characteristics including time to treatment failure (TTF) for EGFR-TKI were evaluated. The T790M mutation analysis of the specimens from the 38 patients detected 30 mutants (79%). The median TTF was 9 months for the patients with pretreatment T790M and 7 months for the patients without the T790M mutation (p = 0.44). When the patients with T790M were divided into strongly positive and modestly positive subgroups in terms of the frequency of positive signals observed using CH technique, the 7 patients with strong positivity had a TTF that was significantly longer than that of the 8 patients without T790M (p = 0.0097) and of the 23 patients with modest positivity (p = 0.0019). Our highly sensitive CH method showed that a subgroup of non-small-cell lung cancer patients with the EGFR mutation harbored the rare T790M allele before EGFR-TKI treatment. A high proportion of T790M allele may define a clinical subset with a relatively favorable prognosis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053559410

Download citation: RISBibTeXText

PMID: 22899358

DOI: 10.1097/jto.0b013e3182653d7f


Related references

Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non-Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR. Clinical Cancer Research 21(15): 3552-3560, 2016

The impact of the tumor shrinkage by initial EGFR inhibitors according to the detection of EGFR-T790M mutation in patients with non-small cell lung cancer harboring EGFR mutations. Bmc Cancer 18(1): 1241-1241, 2018

Osimertinib for advanced non-small cell lung cancer harboring EGFR mutation exon 20 T790M, acquired resistant mutation for first- or second-generation EGFR-TKI. Journal of Thoracic Disease 9(3): 470-473, 2017

Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403. Clinical Lung Cancer 18(2): 241-244, 2016

134O_PR: Plasma ctDNA analysis for detection of EGFR T790M mutation in patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (aNSCLC). Journal of Thoracic Oncology 11(4 Suppl.): S153-S154, 2016

A phase II trial of gefitinib monotherapy in pretreated patients with advanced non-small cell lung cancer not harboring activating EGFR mutations: implications of sensitive EGFR mutation test. Cancer ChemoTherapy and Pharmacology 75(6): 1229-1236, 2015

A phase II trial of EGFR-TKI readministration with afatinib in advanced non-small-cell lung cancer harboring a sensitive non-T790M EGFR mutation: Okayama Lung Cancer Study Group trial 1403. Cancer ChemoTherapy and Pharmacology 82(6): 1031-1038, 2018

Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clinical Cancer Research 17(6): 1616-1622, 2011

Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naïve patients with non-small cell lung cancer harboring EGFR mutations. Oncotarget 8(40): 68123-68130, 2017

Ultra-sensitive EGFR T790M detection as an independent prognostic marker for lung cancer patients harboring EGFR del19 mutations and treated with first-generation TKIs. Clinical Cancer Research 2019, 2019

P3.01-80 Retrospective Analysis of the Impact of Egfr T790M Mutation Detection by Re-Biopsy in Patients with Nsclc Harboring Egfr Mutations. Journal of Thoracic Oncology 13(10): S897-S898, 2018

Highly sensitive detection of EGFR T790M mutation in pre-TKI specimens of EGFR-mutated NSCLC: in cis, in trans, or a different clone?. Journal of Thoracic Oncology 8(3): E26-E27, 2013

Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation. Clinical Lung Cancer 18(6): 698-705.E2, 2017

The impact of intermittent versus continuous exposure to EGFR tyrosine kinase inhibitor on selection of EGFR T790M-mutant drug-resistant clones in a lung cancer cell line carrying activating EGFR mutation. Oncotarget 7(28): 43315-43323, 2016

P3.02b-026 Association of Egfr Exon 19 Deletion and Egfr-Tki treatment duration with Frequency of T790M Mutation in Egfr-Mutant Lung Cancer Patients. Journal of Thoracic Oncology 12(1): S1201-S1202, 2017