+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ 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

Most T790M mutations are present on the same EGFR allele as activating mutations in patients with non-small cell lung cancer



Most T790M mutations are present on the same EGFR allele as activating mutations in patients with non-small cell lung cancer



Lung Cancer 108: 75-82



The T790M and C797S mutations of the epidermal growth factor receptor gene (EGFR) confer resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), respectively, in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR. C797S has been identified in cis or in trans with T790M in tumor specimens from patients who experienced treatment failure with first- and third-generation EGFR-TKIs. The allelic relation between T790M and activating mutations of EGFR has not been well characterized, however. We have now developed a digital polymerase chain reaction (dPCR)-based method for determination of the allelic relation between two types of EGFR mutation (T790M and either C797S or an activating mutation). Seven clinical NSCLC specimens and two NSCLC cell lines harboring both an activating mutation and T790M were analyzed with this new method to identify the allelic relation between these EGFR mutations. The median ratio of the number of alleles positive for both an activating mutation and T790M to the number of T790M-positive alleles was 97.1% (range, 90.0-100%). Confirmatory analysis by next-generation sequencing yielded a corresponding value of 96.7% (range, 89.1-99.5%). Our dPCR method thus reliably identifies the allelic relation between two EGFR mutations in a quantitative manner. Almost all T790M mutations were detected in cis with activating mutations of EGFR regardless of the de novo or acquired status of T790M, with cancer cells harboring T790M and activating mutations on the same allele appearing to be selected and enriched during EGFR-TKI treatment.

Please choose payment method:






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

Accession: 059990058

Download citation: RISBibTeXText

PMID: 28625653

DOI: 10.1016/j.lungcan.2017.02.019


Related references

Clinical activity of ASP8273 in Asian patients with non-small-cell lung cancer with EGFR activating and T790M mutations. Cancer Science 109(9): 2852-2862, 2018

Clinical Outcomes and Secondary Epidermal Growth Factor Receptor (EGFR) T790M Mutation among First-line Gefitinib, Erlotinib and Afatinib-treated Non-small Cell Lung Cancer Patients with Activating EGFR Mutations. International Journal of Cancer 2018, 2018

High ratio of T790M to EGFR activating mutations correlate with the osimertinib response in non-small-cell lung cancer. Lung Cancer 117: 1-6, 2018

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

Coexistence of EGFR T790M mutation and common activating mutations in pretreatment non-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer 94: 46-53, 2016

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs. Oncotargets and Therapy 10: 2267-2279, 2017

Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clinical Cancer Research 17(5): 1160-1168, 2011

EGFR C797S, EGFR T790M and EGFR sensitizing mutations in non-small cell lung cancer revealed by six-color crystal digital PCR. Oncotarget 9(100): 37393-37406, 2019

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

Should EGFR tyrosine kinase inhibitors be used in non-small cell lung cancer in the absence of EGFR mutations? No, EGFR TKIs should be reserved for patients with EGFR mutations. Clinical Advances in Hematology and Oncology 14(1): 41, 44-5, 2016

Comparison of detection methods of EGFR T790M mutations using plasma, serum, and tumor tissue in EGFR-TKI-resistant non-small cell lung cancer. Oncotargets and Therapy 11: 3335-3343, 2018

Osteoblastic response in patients with non-small cell lung cancer with activating EGFR Mutations and bone metastases during treatment with EGFR kinase inhibitors. Journal of Thoracic Oncology 5(3): 407-409, 2010

AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations. Bmc Cancer 16: 491, 2017

C797S and T790M EGFR Mutations in Non-Small Cell Lung Cancer: In Trans or in Separate Clones?. Journal of Thoracic Oncology 13(2): E21-E22, 2018

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