scholarly journals Genome-wide analysis of microRNA signature in lung adenocarcinoma with EGFR exon 19 deletion

2015 ◽  
Author(s):  
Lixia Ju ◽  
Mingquan Han ◽  
Xuefei Li ◽  
Chao Zhao
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Wild Type ◽  
Lung Cancer Patients ◽  
Whole Genome Microarray ◽  
Exon 19 Deletion ◽  
The Difference ◽  
Exon 19

AbstractPurposeThe findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and microRNAs can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer.Materials and methodsIn this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and its wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we have detected the microRNAs expression in serum of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type.ResultsThe expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type.ConclusionsIt is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 can be further explored for potential predictor and targeted biomarker when it is difficult to get the tumors.

Molecular changes in epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) biopsies at time of progression compared to initial biopsy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22066-e22066
Author(s):  
G. Speranza ◽  
V. Cohen ◽  
J. S. Agulnik ◽  
G. Chong ◽  
F. Meilleur ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Kinase Inhibitors ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Missense Mutations ◽  
Molecular Changes ◽  
Mutational Status ◽  
Exon 19 Deletion ◽  
Exon 19

e22066 Background: EGFR mutations predict sensitivity and clinical outcome to tyrosine kinase inhibitors (TKI) in NSCLC. The two most commonly described mutations are Exon 19 deletion and Exon 21 L858R missense mutations. Genetic alterations over time have been described in other tumour types, but studies assessing EGFR genotypic changes with lung cancer progression are lacking. We sought to compare EGFR mutational status from lung tumors at time of recurrence or progression with the primary tumor. Methods: Using the Jewish General Hospital lung cancer database, of all patients diagnosed with NSCLC since 1999, those with biopsies at two different points in time were identified. All tumour samples were genotyped for EGFR exons 19 and 21 mutations using denaturing high performance liquid chromatography (dHPLC). Results: 29 patients were identified. Data for 12 patients, whose time of recurrence or progression varied between 4 months and 6 years, are available at this time. Of 12 patients, one had EGFR exon 19 mutation at time of diagnosis. One patient who initially displayed no EGFR mutation was found to have an exon 19 deletion at time of recurrence. The one with exon 19 at time of initial diagnosis continued to express exon 19 in the second biopsy. Conclusions: To our knowledge, this is the only study assessing changes in molecular genotype using dHPLC between primary and recurrent or progressive lung cancer biopsy specimens. Although sample size is small, it is evident that changes in EGFR mutational status can occur. Further prospective studies are required to determine how commonly molecular changes occur. No significant financial relationships to disclose.

scholarly journals Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Deng Pan ◽  
Dapeng Zhou ◽  
Weijing Cai ◽  
Weibo Wu ◽  
Wen Ling Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Chinese Population ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Lung Cancer Patients ◽  
Hla Class I Molecules

Abstract Background Mutant peptides presented by cancer cells are superior vaccine candidates than self peptides. The efficacy of mutant K-Ras, P53 and EGFR (Epidermal Growth Factor Receptor) peptides have been tested as cancer vaccines in pancreatic, colorectal, and lung cancers. The immunogenicity of EGFR Del19 mutations, frequent in Chinese lung adenocarcinoma patients, remains unclear. Results We predicted the HLA binding epitopes of Del19 mutations of EGFR in Chinese lung adenocarcinoma patients with NetMHC software. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the EGFR-reactive IgG in lung cancer patients. Del19 mutations may be presented by multiple HLA Class I molecules, with delE746_A750 presented by 37.5% of Chinese population. For HLA Class II molecules, Del19 mutations of EGFR may be presented by multiple HLA-DRB1 molecules, with delE746_A750 presented by 58.1% of Chinese population. Serum reactivity to wild type EGFR protein was significantly higher in patients with Del19 EGFR mutations than those with EGFR L858R point mutation or with EGFR wild type genotype. Conclusions These findings suggest that Del19 mutations of EGFR, with an estimated frequency of 40% in Chinese lung adenocarcinoma patients, may serve as unique targets for immunotherapy in Chinese lung cancer patients.

Validation study of direct sequencing and PCR-invader for detecting EGFR mutations in non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8094-8094
Author(s):  
Y. Naito ◽  
K. Goto ◽  
H. Kenmotsu ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Pcr Amplification ◽  
The Other ◽  
Egfr Mutations ◽  
Wild Type ◽  
Highly Sensitive ◽  
Formalin Fixed Paraffin Embedded ◽  
Exon 19 Deletion ◽  
Exon 19

8094 Background: EGFR mutation is both a predictive and prognostic factor for NSCLC treated with EGFR-TKI. Although new, highly sensitive methods for detecting EGFR mutations are currently available, these methods have not been validated. Methods: To validate direct sequencing and PCR-invader for detecting EGFR mutation, we analyzed 124 NSCLC by both methods concomitantly. Tumor tissues were obtained by surgical resection. Formalin-fixed paraffin-embedded specimens were prepared to analyze EGFR mutation. In direct sequencing, Exon 18, 19, and 21 of the EGFR gene were amplified, and PCR amplification products were sequenced directly (Mitsubishi Chemical Medience Corporation). PCR-invader was performed using the invasive cleavage of probe oligonucleotides to detect 10 mutations including Exon 18, 19, 20, 21 (BML incorporation). Results: EGFR mutations were detected in 51 patients (41%) by direct sequencing and 56 (45%) by PCR-invader. Discordance between two methods was found in 12 patients (10%). Exon 19 deletion was detected in 18 and 22 patients respectively. Exon 21 L858R was detected in 30 and 32 patients respectively. Each mutation in exon 19 deletions or L858R detected by direct sequencing could also be identified by PCR-invader. Overall 45 mutations were concordant by both methods. In two patients who received gefitinib, one patient with wild type by both methods did not respond to gefitinib. On the other hand, the other patient expressing Exon 19 deletion by PCR-invader but regarded as wild type by direct sequencing responded to gefitinib monotherapy. Conclusions: Discrepancy between two methods for detecting EGFR mutation was demonstrated and PCR-invader seems to be more sensitive. Further investigation including other highly sensitive methods is currently underway. No significant financial relationships to disclose.

Higher incidence of EGFR exon 19 deletion in younger (age 40 or younger) patients with adenocarcinoma of the lung.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7044-7044
Author(s):  
Eri Sugiyama ◽  
Koichi Goto ◽  
Genichiro Ishii ◽  
Shigeki Umemura ◽  
Kiyotaka Yoh ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lung Adenocarcinoma ◽  
Signet Ring Cell ◽  
Egfr Mutations ◽  
Cell Component ◽  
Younger Patients ◽  
Signet Ring ◽  
Exon 19 Deletion ◽  
Ring Cell ◽  
Exon 19

7044 Background: The proportion of younger patients (≤ 40 years) with lung cancer is reported to be 2-5%. The most frequent histologic type of them is adenocarcinoma, however little is known about the pathological and molecular characteristics of younger patients with lung adenocarcinoma. Methods: Between July 1992 and April 2011, a total of 7443 patients were diagnosed as lung cancer in National Cancer Center Hospital East and 165 patients of whom (2.2%) who were 40 years or younger were identified. Among them, 44 patients with adenocarcinoma who underwent surgical resection were selected for this study. In addition, 185 elderly patients with > 40 years who underwent surgical resection matching gender and smoking status were selected as a control group. Histological predominant growth pattern and any coexisting variant pattern, the status of EGFR mutations were compared between these two groups. Results: The median age in ≤ 40 years patients was 37 years (range, 21 to 40 years) and that in elderly patients was 68 years (range, 42 to 83 years). Between these two groups, there were no significant differences in the distribution of histological predominant growth patterns (lepidic; 31.8% vs. 26.5%, papillary; 34.1% vs. 37.3%, acinar; 9.1% vs. 16.2%, and solid; 25.0% vs. 20.0%, p=0.78) and the incidence of EGFR mutations (40.9% vs. 45.9%; p=0.55). However, signet-ring cell component were significantly found in the younger patients than elderly (11.4% vs. 0%; p<0.01). The incidence of EGFR exon 19 deletion was significantly higher in younger patients than elderly, in contrast, that of EGFR exon 21 L858R was significantly higher in elderly patients (exon 19 del; 31.7% vs. 18.9%, L858R; 4.6% vs. 25.4%, p=0.0091). Three of 17 adenocarcinomas (17.7%) with EGFR-wild type in younger patients showed positive for ALK translocation. Conclusions: Younger patients with lung adenocarcinoma showed significantly higher proportion of EGFR exon 19 deletion genotype and containing histologically signet-ring cell component comparing with elderly patients. EGFR exon 19 deletion genotype may be related to pathogenesis of lung adenocarcinoma in younger patients.

Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20565-e20565 ◽  
Author(s):  
Ruben Salanova ◽  
Julio C Calderazzo Pereyra ◽  
Laura Leguina ◽  
Asuncion Bena ◽  
Mariana Barberis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Mutational Status ◽  
Alk Positive ◽  
Egfr Mutant ◽  
Exon 19

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p > 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.

Concurrent somatic alterations of TP53 and RB1 in Chinese lung adenocarcinoma with or without EGFR mutations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21526-e21526
Author(s):  
JUN WANG ◽  
Gang Chen ◽  
Bicheng Zhang ◽  
Jianguo Sun ◽  
Jing Liang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Wild Type ◽  
Mutational Status ◽  
Significant Difference ◽  
Somatic Alterations ◽  
Egfr Mutant ◽  
Mutant Egfr

e21526 Background: Endothelial growth factor receptor (EGFR)-mutant lung adenocarcinoma displays diverse responses to tyrosine kinase inhibitor therapy. Concurrent somatic alterations represent different biological substantial proportion of patients with EGFR mutations and impacts their prognosis. Methods: We conducted this retrospective study to clarify the comprehensive concurrent genetic alterations of TP53 and RB1 and tumor mutational burden (TMB) in 712 EGFR-mutant or EGFR-wild type lung adenocarcinoma by next generation sequencing-based gene panel tests. Results: EGFR was the most frequently mutated gene altered in 58.0% (413/712) of lung adenocarcinoma, followed by TP53 altered in 56.7%, KRAS altered in 13.3%, and RBM10 altered in 11.2% of all patients. Concurrent genetic alteration of TP53 and RB1 is more likely to be found in EGFR-mutant patients than in EGFR-wild type patients, with a frequency of 11.4% (45/413) and 4.3% (13/299), respectively (p = 0.003). However, the frequency of TP53 and RB1 concurrent alteration was similar in lung cancer with sensitive EGFR mutation compared to those with non-sensitive mutation (10.5% versus 11.6%). TP53 mutation was most frequently found in patients with RB1 mutation (58/61), irrespective of EGFR mutational status. Furthermore, significant difference was found regarding median TMB in patients with mutant EGFR compared to those with non-mutant EGFR (3.8 versus 4.3; p < 0.001). Median TMB was higher for patients with TP53 and RB1 concurrent alteration than those without concurrent alteration in all patients (5.4 versus 4.3, p = 0.018). Conclusions: Our data showed that high prevalence of concurrent somatic alterations of TP53 and RB1 genes among lung adenocarcinoma patients with EGFR mutations, which might help understand several key biological processes and develop potential therapeutic strategies.

Prognostic implication of the EGFR gene mutations in a large cohort of Japanese patients with early stage lung adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7574-7574 ◽  
Author(s):  
T. Kosaka ◽  
Y. Yatabe ◽  
R. Onozato ◽  
T. Mitsudomi
Keyword(s):  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Prognostic Impact ◽  
Egfr Gene ◽  
Deletion Mutations ◽  
Exon 19 Deletion ◽  
Never Smokers ◽  
Exon 19

7574 Background: Prognostic impact of epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinoma remains controversial. We examined a large cohort of lung adenocarcinoma resected in a single institution for EGFR mutations and evaluated its prognostic implication. Methods: We analyzed 402 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection at our department, from May 2000 through December 2005. Total RNA was extracted and direct sequencing of exons 18–21 of EGFR gene was performed after reverse transcription - polymerase chain reaction. KRAS and TP53 gene mutations were also analyzed in 209 adenocarcinoma patients from this cohort. Results: We found that 196 patients (49%) had EGFR mutations. Of them, exon 19 deletion mutations were 83 (42%) and L858R mutations were 92 (47%). EGFR mutations were significantly frequent in female (P<0.0001), never smokers (P<0.0001), and well to moderately differentiated adenocarcinoma (P<0.0001). In 347 patients who were not treated with gefitinib, prognostic effect of EGFR mutations was evaluated. Patients with EGFR mutations survived for a longer period than those without the mutations after surgery in univariate analysis (P=0.0046, log rank test). We did not detect any difference in overall survival between the patients with exon 19 deletion mutations and those with L858R mutations (P=0.3962). There were tendencies that patients with KRAS mutations or TP53 mutations survived for a shorter period than those without mutations, although there was no statistical significance (P=0.2534 and 0.0859). Multivariate analysis using the Cox proportional hazards model revealed that never smokers (P=0.0253) and disease stage (P<0.0001) were independent prognostic factors. However, all gene mutations were not independent prognostic factors (EGFR; P=0.4763, KRAS; P=0.7998, TP53; P=0.3464). Conclusion: EGFR mutations were not independently associated with prognosis of patients with early stage adenocarcinoma of the lung. Furthermore, there was no difference between exon 19 deletion mutations and L858R mutations in their prognostic impact. No significant financial relationships to disclose.

Multicenter prospective trial of customized erlotinib for advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations: Final results of the Spanish Lung Cancer Group (SLCG) trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8023-8023
Author(s):  
B. Massuti ◽  
T. Morán ◽  
R. Porta ◽  
C. Queralt ◽  
F. Cardenal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Negative Impact ◽  
Cox Model ◽  
Prospective Trial ◽  
Complete Response ◽  
Egfr Mutations ◽  
First Line ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Exon 19

8023 Background: The purpose of the study was to evaluate the efficacy of erlotinib and the feasibility of screening for EGFR mutations in advanced NSCLC p (chemonaive or relapsed after 2 prior chemotherapy regimens). Methods: Exon 19 deletions and L858R mutations in tumor and paired serum DNA were assessed in one central laboratory, using three different techniques. Results: From April 2005 to December 2008, 2507 p were screened. EGFR mutations were detected in 358 p; 217 were entered on the trial: 158 (72.8%) female; 148 (68.2%) never-smokers; 176 (81.1%) adenocarcinoma; 134 (62.3%) exon 19 deletion, 83 (37.7%) L858R mutation; 112 (51.6%) first-line, 104 (48.4%) second-line. Response in 139/197 evaluable p (70.6%); complete response (CR) in 24 p (12.2%). Odds ratio for response: 3 for p with exon 19 deletion (P=0.001). Time to progression (TTP): 14 months (m). Median survival (MS): 27 m. MS according to response shown in table. Cox model for TTP showed that male gender (hazard ratio [HR], 2.3; P=0.001), L858R mutation (HR, 1.8; P=0.008), and mutated EGFR in serum (HR,1.6; P=0.03) had a negative impact. Conclusions: A multicenter study of customized erlotinib, using a central screening laboratory, is feasible and shows the outstanding benefit to p for selecting erlotinib treatment based on EGFR mutation status. The SLCG has initiated a randomized trial of first-line erlotinib vs chemotherapy. [Table: see text] No significant financial relationships to disclose.

Genetic evolution of EGFR and the clonal origin of adenocarcinomas exhibiting various degrees of bronchioloalveolar carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22050-e22050
Author(s):  
W. Zhong ◽  
X. Yang ◽  
A. Guo ◽  
J. Su ◽  
X. Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Distant Metastases ◽  
Genetic Alterations ◽  
Bronchioloalveolar Carcinoma ◽  
Egfr Mutations ◽  
Lung Field ◽  
Wild Type ◽  
Activating Mutations ◽  
Single Clone

e22050 Background: EGFR mutations may accumulate during multistage progression of bronchioloalveolar carcinoma (BAC), leading to heterogeneity within the tumor. Moreover, intrapulmonary emersions are the predominant sites of BAC progression in the absence of other distant metastases. In cases of emerging bilateral lung lesions during the follow-up to complete resection, the issue of how to differentiate between lesions originating from multifocal BACs or distant metastases/local recurrence is an important and unresolved issue. This study was performed to determine whether sequential adenocarcinoma with BAC features emerges in the lung field arises from a single clone or multiple clones in the same individual. Methods: Samples of adenocarcinomas exhibiting various degrees of BAC were obtained by thoracotomy. Sequential specimens were obtained on detection of novel lesions in the lung field. Genomic DNA was extracted from the specimens, and the presence of activating mutations in EGFR was analyzed by direct sequencing. Our pathological findings, sequential imaging, and EGFR sequence data were compared to monitor evidence of cancer evolution. Results: Based on an analysis of EGFR in tumor specimens from 428 lung cancer patients, fifteen cases of sequential BAC-related adenocarcinoma obtained by thoracotomy were identified. Together with alterations in BAC/adenocarcinoma components, the EGFR-TKI untreated series with at least one episode of EGFR-activating mutations represented three typical models: no significant EGFR evolution for a single clone, genetic alterations from mutant to wild-type EGFR for multifocal lesions, and a switch from wild-type to mutant EGFR, which might exhibit uncertain circumstances of cancer progression. Conclusions: Genetic analysis in conjunction with pathological and radiological diagnoses can be used to explore the origin of multifocal BAC. The single clone model indicates subsequent disease progression, whereas genetic alterations from mutations to wild-type EGFR are suggestive of secondary primary carcinoma. When additional lesions emerge after radical resection of BAC-related lung cancer, sequential tumor samples should be obtained for further evaluation. No significant financial relationships to disclose.

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