Clinical screening assay for EGFR exon 19 mutations using PNA-clamp smart amplification process version 2 in lung adenocarcinoma

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.

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MRI-Based Radiomics Nomogram as a Potential Biomarker to Predict the EGFR Mutations in Exon 19 and 21 Based on Thoracic Spinal Metastases in Lung Adenocarcinoma

Academic Radiology ◽

10.1016/j.acra.2021.06.004 ◽

2021 ◽

Author(s):

Ran Cao ◽

Yue Dong ◽

Xiaoyu Wang ◽

Meihong Ren ◽

Xingling Wang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Spinal Metastases ◽

Egfr Mutations ◽

Thoracic Spinal ◽

Potential Biomarker ◽

Exon 19

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Uncommon EGFR Exon 19 Mutations Confer Gefitinib Resistance in Advanced Lung Adenocarcinoma

Journal of Thoracic Oncology ◽

10.1097/jto.0000000000000538 ◽

2015 ◽

Vol 10 (6) ◽

pp. e50-e52 ◽

Cited By ~ 5

Author(s):

Simona Coco ◽

Anna Truini ◽

Irene Vanni ◽

Carlo Genova ◽

Camillo Rosano ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Gefitinib Resistance ◽

Exon 19

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LncRNA expression profiles of EGFR exon 19 deletions in lung adenocarcinoma ascertained by using microarray analysis

Medical Oncology ◽

10.1007/s12032-014-0137-y ◽

2014 ◽

Vol 31 (9) ◽

Cited By ~ 14

Author(s):

Yumin Wang ◽

Wei Chen ◽

Jie Chen ◽

Qinshi Pan ◽

Jingye Pan

Keyword(s):

Lung Adenocarcinoma ◽

Microarray Analysis ◽

Expression Profiles ◽

Lncrna Expression ◽

Exon 19

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

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7574 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7574-7574 ◽

Cited By ~ 9

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.

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Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21616 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21616-e21616

Author(s):

Jun Zhao ◽

Zaiwen Fan ◽

Donghong Chen ◽

Minglei Zhuo ◽

Zhen Liang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Chinese Patients ◽

Therapeutic Effects ◽

Significant Difference ◽

Treatment Naïve ◽

Exon 19 Deletion ◽

Egfr Mutant ◽

Egfr Tkis ◽

Exon 19

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p<0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p<0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p<0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.

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