Identification of non-small-cell lung cancer with activating EGFR mutations in malignant effusion and cerebrospinal fluid: Rapid and sensitive detection of exon 19 deletion E746-A750 and exon 21 L858R mutation by immunocytochemistry

Lung Cancer ◽  
2011 ◽  
Vol 74 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Akihiko Kawahara ◽  
Koichi Azuma ◽  
Akiko Sumi ◽  
Tomoki Taira ◽  
Kazutaka Nakashima ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Malignant Effusion ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Exon 19

Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: Distinguishing influence of exon 19 deletion on radiographic features

Lung Cancer ◽  
2012 ◽  
Vol 77 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Akimasa Sekine ◽  
Terufumi Kato ◽  
Eri Hagiwara ◽  
Takeshi Shinohara ◽  
Takanobu Komagata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Tumors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Metastatic Brain Tumors ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
Exon 19

Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring EGFR Exon 19 Deletion and Exon 21 L858R Substitution

Chemotherapy ◽  
2017 ◽  
Vol 62 (3) ◽  
pp. 151-158 ◽  
Author(s):  
Nobuyuki Koyama ◽  
Yasutaka Watanabe ◽  
Yuki Iwai ◽  
Rumi Kawamura ◽  
Chihiro Miwa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Multivariate Analyses ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
Exon 19

Background: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. Methods: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R. Results: Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types. Conclusion: Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.

scholarly journals Histological transformation of lung adenocarcinoma to small cell lung cancer with mutant C797S conferring acquired resistance to osimertinib

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092791 ◽  
Author(s):  
Xiaohui Ren ◽  
Xinfeng Cai ◽  
Jing Li ◽  
Xia Zhang ◽  
Jianfei Yu ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Exon 19 Deletion ◽  
Exon 19

Epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer may initially respond to EGFR tyrosine kinase inhibitors (TKIs), but may subsequently become resistant; however, the resistance mechanisms remain unclear. We report a rare case of acquired resistance to osimertinib associated with transformation to small cell lung cancer (SCLC) with cis-C797S mutation. A man with recurrent lung adenocarcinoma harboring an EGFR exon 19 deletion received erlotinib for 10 months following curative surgery and adjuvant chemotherapy. However, he switched to osimertinib after repeat biopsy showed EGFR exon 19 deletion and T790M mutation leading to erlotinib resistance. His disease progressed after 15 months and repeat biopsy showed SCLC. Next-generation sequencing of peripheral blood detected EGFR exon 19 deletion, T790M mutation, cis-C797S mutation, and RB1 inactivation. The tumor was reduced after four cycles of etoposide and cisplatin and his respiratory symptoms improved. However, computed tomography after six cycles of chemotherapy showed multiple bilateral lung lesions, and single-photon emission computed tomography showed bone metastasis. The patient received paclitaxel plus cisplatin for two cycles with partial response. Because heterogeneous genetic and phenotypic mechanisms of TKI-resistance may occur at different times and locations, histopathological and molecular testing both provide evidence to support appropriate treatment.

scholarly journals The impact of EGFR exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer

2020 ◽  
Vol 9 (4) ◽  
pp. 1149-1158
Author(s):  
Chao Zhao ◽  
Tao Jiang ◽  
Jiayu Li ◽  
Yan Wang ◽  
Chunxia Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
The Impact ◽  
Exon 19

Survival benefit of gefitinib treated non-small-cell lung cancer patients with exon 19 deletion mutations in epidermal growth factor receptor (EGFR), detected by a new sensitive PCR-based method

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10614-10614
Author(s):  
E. Nakajima ◽  
M. Sugita ◽  
R. Dziadziuszko ◽  
M. Tsuboi ◽  
H. Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Benefit ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Deletion Mutations ◽  
Exon 19 Deletion ◽  
Exon 19

10614 Background: As for two common types of EGFR mutations, patients with exon 19 deletion mutations have longer survival than those with the L858R point mutations in exon 21 after treatment with EGFR inhibitors. We have developed a simple, polymerase chain reaction (PCR)-based method to detect exon 19 deletion mutations, and evaluated survival benefit of gefitinib treated patients with exon 19 deletion mutations versus patients without these mutations. Patients and methods: Tumor tissue was microdissected under stereoscopic microscopy from formalin-fixed paraffin-embedded sections, and DNA was extracted from tumor cells with DNeasy (Qiagen). Our method consisted of two different semi-nested PCRs with the deletion screening PCR and the common deletion specific PCR. All of the known deletions present in cell lines were detected by this method without direct sequencing. The result was validated by sequencing of exon 19. 73 non-small-cell lung cancer (NSCLC) Japanese patients treated with gefitinib were analyzed with this method. Study group consisted of 28 females (38%), 29 never smokers (40%) and 57 patients with adenocarcinoma (78%). Results: The PCR-based method detected mutations at mutant to wild type DNA copy ratio of 1/600, and in samples as small as 30 ng of purified DNA. Exon 19 deletion mutations were found in 25 (34%) patients. This method was more sensitive than conventional sequencing. The sequencing was performed in 19 patients with mutations and could not detect 3 deletions. Among 60 assessable patients 14 had overall response (23%). Objective response rates to gefitinib were observed in 7/21 patients with exon 19 deletion mutations (33%), and 7/39 patients without exon 19 deletion mutations (17%) (P = .211). Patients with exon 19 deletion mutations survived significantly longer than those without exon 19 deletion mutations (P = .017). Conclusions: The PCR-based method to detect exon 19 deletion mutations is cost effective and very sensitive, compared to previously described methods. We demonstrated survival benefit in NSCLC patients with exon 19 deletion mutations treated with gefitinib, and our PCR-based method is easily applicable for clinical use. No significant financial relationships to disclose.

Coexistence of MET exon 14 mutations with EGFR mutations in non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20636-e20636
Author(s):  
Wen-Feng Li ◽  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Su Jian ◽  
Huajun Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Point Mutations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Relative Resistance ◽  
L858r Mutation ◽  
Nsclc Patients

e20636 Background: Activation of MET oncogene as the result of amplification or activation MET exon 14 mutations represents an emerging molecular target for non-small cell lung cancer (NSCLC) treatment. MET exon 14 mutations account for 1.0% in Chinese NSCLC patients. However, few data have been reported on the coexisting of MET exon 14 mutations and EGFR mutations in NSCLC. Moreover, the clinicopathological characteristics and targeted therapy of these MET/ EGFR-coexisting patients remain elusive. Methods: Next-generation sequencing was performed on the DNA of 969 patients and Sanger sequencing was conducted on cDNA of 621 patients for MET exon 14 mutations in NSCLCs. EGFR mutations were determined by direct DNA sequencing. Results: Fifteen patients harbored positive MET exon 14 mutations. Frequency of concomitant EGFR and MET exon 14 mutations was 0.2%(3/1590). 3 patients with concomitant MET exon 14 mutation and EGFR activating mutation were all female, never smokers and adenocarcinoma. Their stagings were stageⅠB (n = 1) and stage Ⅳ(n = 2). The stage ⅠB patient harboring concomitant MET exon 14 skipping and EGFR L858R mutation did not relapse 2 years after operation. The other two stage Ⅳ patients received first-line gefitinib. Case one harbored concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR exon 19 deletion, and showed resistance to gefitinib with progression free survival(PFS) of 2 weeks and overall survival(OS) of 1 month. Case two had concomitant MET exon 14 point mutations (IVS13-36G > A) and EGFR L858R mutation. Meanwhile, she also had both METamplification and c-Met overexpression at the baseline. She showed partial response (PR) to gefitinib with 3.8 months PFS. Then she was enrolled in a clinical trial (NCT02374645) to receive volitinib plus gefitinib on December 20, 2016. Initial response was good PR on January 24, 2017. Only grade 1 rash was observed. Conclusions: Coexisting MET exon 14 /EGFR mutation is an uncommon molecular event in NSCLC patients. Such coexisted patients might show relative resistance to EGFR inhibitor. However, combination of MET and EGFR inhibitors will be potentially a good strategy to overcome such a relative resistance for MET exon 14 /EGFR co-mutant patients.

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