Epidermal Growth Factor Receptor Double Activating Mutations Involving Both Exons 19 and 21 Exist in Chinese Non-small Cell Lung Cancer Patients

Zhang, Guochun; Lin, Jun; Wang, Z; Zhou, Qing; Xu, Chenchen; Zhu, Jun; Wang, K; Xn, Yang; G, Chen; Yang, Jing; Yj, Huang; Liao, Ri-Qiang; Wu, Yi‐Long

doi:10.1016/j.clon.2007.04.006

Cited by 48 publications

(44 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Relevant references from the searched studies (6 references) were also reviewed. In total, 18 patients with EGFR Del-19 + L858R mutations that received EGFR-TKIs were identified between January 2002 and January 2015 (Table I) (17)(18)(19)(20)(21)(22). Of these 18, 16 patients were assessed based on RECIST (15) and 2 patients were not evaluated.…”

Section: Discussionmentioning

confidence: 99%

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Yang

Zhang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be effective treatments for advanced non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations, including exon 19 deletion and exon 21 L858R mutations. However, with the development of EGFR mutation detection assays, patients with complex EGFR mutations are emerging, and their response to EGFR-TKIs remains unclear. The present study reports a case of a 62-year-old, non-smoking female patient with advanced NSCLC, presenting with concurrent EGFR 19+21 sensitizing mutations, who had a poor response to the first-line EGFR-TKI erlotinib and succumbed 5 months subsequent to diagnosis. Furthermore, the present study performed a literature review, and 18 patients with complex EGFR 19+21 mutations that had received EGFR-TKIs were identified. The majority of these patients responded well to EGFR-TKIs. To the best of our knowledge, the present case is the first to report a patient with lung adenocarcinoma with complex EGFR 19+21 sensitizing mutations that had a poor clinical response to a first-line EGFR-TKI. Despite the 70% response rate of sensitizing EGFR-mutant NSCLCs to EGFR-TKIs, there is still a proportion of patients that experience de novo resistance, and heterogeneity is likely to be important in this resistance mechanism. Therefore, comprehensive genomic detection assays and multi-targeted therapies for patients with NSCLC with complex EGFR mutations require additional investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Yang

Zhang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…Complex EGFR mutations can appear before treatment [7,8,13] or be induced by TKI sequentially [21][22][23]. For example, a novel high resistance mutation, T790M, is an acquired mutation after EGFR TKI treatment [22,23].…”

Section: Progression-free Survival and Overall Survival After Egfr Tkmentioning

confidence: 99%

“…Concomitant EGFR mutations have been termed "complex mutations" [20]. A second mutation may substantially alter the biological properties of the mutant EGFR and sensitivity to TKIs [21]. For example, T790M is a noteworthy acquired EGFR mutation after EGFR TKI treatment in patients with L858R or del-19, which confers resistance to EGFR TKI treatment [22,23].…”

Section: Introductionmentioning

confidence: 99%

Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern

Chang

Hsu

et al. 2008

The Oncologist

View full text Add to dashboard Cite

Background. Epidermal growth factor receptor (EGFR) mutations are usually detected in lung adenocarcinoma and are associated with a response to EGFR tyrosine kinase inhibitors (TKIs). However, not all EGFR mutations have similarly high clinical response rates. This study aimed to investigate the clinical characteristics and response to gefitinib in lung adenocarcinoma patients with complex EGFR mutations.Materials and Methods. Three hundred thirty-nine specimens of lung adenocarcinoma from patients treated with gefitinib were collected for EGFR sequencing. Nineteen patients with complex EGFR mutations were enrolled for the study after excluding three patients with the EGFR T790M mutation, which confers resistance to gefitinib.

show abstract

“…EGFR double mutations have been reported in previous studies (49)(50)(51)(52)(53)(54)(55). For example, Zhang et al (54) found that 6.5% (5/77) of lung adenocarcinoma patients possessed double mutations. Masago et al (51) found that this figure was 4.4% (4/90).…”

Section: Discussionmentioning

confidence: 89%

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

et al. 2017

View full text Add to dashboard Cite

Abstract. Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different driver mutants, including the serine/threonine-protein kinase B-raf (BRAF) inhibitor dabrafenib, which has exhibited promising efficacy for treating patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients carrying mutations that may be treated using targeted therapies is important. However, the methods of molecular detection presently applied in clinical practice, particularly detection of BRAF in NSCLC patients, require further investigation. Therefore, more sensitive and economic methods are required. The present study applied the competitive allele-specific TaqMan polymerase chain reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive patients with lung adenocarcinoma, and analyzed the association between the mutation rates and patients' clinicopathological features. 51.4% (74/144) cases were identified harboring EGFR mutations. A total of 40.3% (58/144) patients carried sensitizing mutations (exon 19 deletion or L858R) and 14.6% (21/144) carried T790M mutations. 6.9% (10/144) mutation-positive patients were double-mutated. Total EGFR mutation rate was significantly increased in female compared with that of males (60.9 vs. 43.8%, P<0.05), in non-smokers compared with that of smokers (62.8 vs. 34.5%, P<0.05). In total, 8.3% (12/144) patients were identified with BRAF mutations. 16.7% were V600E (2/12) and 83.3% (10/12) were non-V600E mutants. Among the 10 non-V600E mutations, D594G accounted for 90.0% (9/10) and G469A accounted for 10.0% (1/10). Statistical analysis demonstrated that the BRAF mutation rate was not associated with any of the following clinicopathological features: Sex, age, smoking history, clinical stages, distant metastasis, differentiation degree, tumor size and regional lymph node metastasis (P≥0.05). CastPCR technology is a robust method with high sensitivity for the molecular detection of EGFR and BRAF mutations in clinical formalin-fixed paraffin-embedded samples.

show abstract

Epidermal Growth Factor Receptor Double Activating Mutations Involving Both Exons 19 and 21 Exist in Chinese Non-small Cell Lung Cancer Patients

Cited by 48 publications

References 24 publications

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature

Good Response to Gefitinib in Lung Adenocarcinoma of Complex Epidermal Growth Factor Receptor (EGFR) Mutations with the Classical Mutation Pattern

Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan polymerase chain reaction in lung adenocarcinoma

Contact Info

Product

Resources

About