p53 and EGFR gene mutations
in malignant tumors of the lung

Relevance: Increased incidence of lung cancer globally and in Kazakhstan, lack of screening in hereditary cases, high mortality, and low survival of patients necessitate the study of the molecular genetic causes of the disease. At present, gene mutation studies for lung cancer diagnostics are expanding. However, many gene mutations revealed remain undercovered in the scientific literature, and there is not enough data on their prognostic and diagnostic value. The purpose of the study was to discover the specifics of the р53 gene mutations and reveal the EGFR exon 19 deletions and exon 21 L858R mutations in malignant tumors of the lung of various histogenesis. Methods: The mutations were studied in tumors (200 samples) and adjacent tissue (200 samples) of patients with lung cancer (squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung) by polymerase chain reaction (PCR), electrophoresis, and EcoR1- and Pst1-restriction of samples after p53 gene fragments and cDNA amplification and mRNA revertase treatment. Another 263 lung cancer samples were evaluated by real-time PCR for EGFR exon 19 deletions and EGFR exon 21 L858R mutations. Results: The p53 gene was not expressed in 50% of SCC and adenocarcinoma of the lung samples. Restriction revealed p53 mRNA mutations in 100% of SCC and 75% of ADC samples. p53 exon-intron 5-6 was mutated in 50% of ADC and 70% of SCC samples, exon-intron 7-9 – in 60% of SCC cases. EGFR exons 19 and 21 mutations found in 65 of 263 lung tumor samples were associated with increased sensitivity to EGFR tyrosine kinase inhibitors. Conclusion: The p53 gene mutations revealed in most samples of SCC and ADC of the lung could be used to diagnose lung cancer and predict its severity. The identified EGFR mutations allow predicting the effectiveness of targeted therapy

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Proportion of Mutation of Epidermal Growth Factor Receptor (EGFR) Genes from Tissue Biopsy and Liquid Biopsy ctDNA in Lung Adenocarcinoma

Jurnal Respirologi Indonesia ◽

10.36497/jri.v40i3.118 ◽

2020 ◽

Vol 40 (3) ◽

pp. 150-155

Author(s):

Hendra Taufik ◽

Noni Novisari Soeroso ◽

Setia Putra Tarigan ◽

Erna Mutiara

Keyword(s):

Lung Cancer ◽

Growth Factor Receptor ◽

Gene Mutations ◽

Circulating Tumor Dna ◽

Cross Sectional Study ◽

Egfr Mutations ◽

Cross Sectional ◽

Lung Cancer Patients ◽

Tissue Biopsy ◽

Exon 19

Backgrounds: In recent years, circulating tumor DNA (ctDNA) has emerged as a specific and sensitive blood-based biomarker to detect EGFR mutations. This study aims to determine the diagnostic accuracy of ctDNA in detecting EGFR gene mutations in adenocarcinoma lung cancer. Methods: This study was a cross-sectional study with the subjects were adenocarcinoma lung cancer patients from histopathology or cytology examination and examined EGFR mutations from plasma tissue biopsy and ctDNA specimens from April 2018 to February 2019 in several hospitals in the Medan City. Results: There were 100 data have been collected, with male were 71 subjects and female were 29 subjects. Found 20 mutations, single mutations of tissue biopsy were 19 cases, del exon 19 were 12 cases, mutation in exon 21 (L858R) were 6 cases, mutation exon 21 (L861Q) was 1 case, del exon 19 and 21 (L861Q double mutations) was 1 case. From plasma ctDNA examination EGFR mutations were found 15 cases, del exon 19 were 12 cases and del exon 21 (L858R) were 3 cases. Conclusions: The highest proportion of EGFR mutations by sex were women from tissue biopsy or ctDNA, the most often frequency of EGFR mutations from tissue biopsy and ctDNA in single mutations and exons19. (J Respir Indo. 2020; 40(3): 150-5)

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Spectrum of EGFR mutations associated with non-small cell lung cancer in an Asian Chinese population

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20055 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20055-20055

Author(s):

C. Wong ◽

W. Chan ◽

H. Lam ◽

W. Chan ◽

L. Wang ◽

...

Keyword(s):

Lung Cancer ◽

Base Pair ◽

Lung Tumor ◽

Chinese Patients ◽

Bronchioloalveolar Carcinoma ◽

Egfr Mutations ◽

Nucleotide Sequencing ◽

Asian Ethnicity ◽

Base Pair Deletion ◽

Exon 19

20055 Background: Somatic mutations in tyrosine kinase (TK) domain of the EGFR gene, predicting for sensitivity to TK inhibition therapy, are over-represented in lung cancer with adenocarcinoma or bronchioloalveolar histology, non-smokers, female gender and East Asian ethnicity. Methods: We prospectively screened for EGFR mutations at exons 19–21 on micro-dissected specimen enriched for tumor cells by direct nucleotide sequencing in Hong Kong Chinese patients. Results: From May 2005 onwards, a total of 27 patients were analyzed. They comprised 11 males and 16 females with a median age of 67 years. Histological diagnoses were adenocarcinoma (n = 22), bronchioloalveolar carcinoma (n = 4) and squamous cell carcinoma (n = 1). Samples included primary tumor (n = 20) as well as metastatic lesions (n = 7). EGFR mutations were detected in 17 patients (63%), the most common being L858R at exon 21 (n = 7) followed by exon 19 deletions (del(746–750) = 3, del(747–751) = 1, del(747–753) = 3) and G719C at exon 18 (n = 1). Two patients showed novel EGFR mutations, namely 4-base pair insertion deletion at exon 19 leading to substitution of Glu746-Leu747 by Val746-Pro747 and three base pair deletion at exon 18 leading to replacement of Glu709-Thr710 by Asp. Furthermore, two patients showed double mutations, including novel S768I at exon 20 in combination with G719C, and novel K860I at exon 21 in combination with L858R. Finally, one patient showed homozygous del(747–753) as detected by sequencing in both primary lung tumor and brain secondary, which might represent loss of heterozygosity. Conclusions: Similar to other series, two hotspots i.e. exon 19 deletion and L858 account for the majority (82%) of detectable EGFR mutations in our patient population. For the rare and novel variants, it would be of interest to document the clinical responsiveness to TK inhibitors gefitinib and erlotinib, so that a more complete picture of cancer genotype phenotype correlation can be achieved. No significant financial relationships to disclose.

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Re-use of erlotinib in a patient using osimertinib after erlotinib, case report

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211019108 ◽

2021 ◽

pp. 107815522110191

Author(s):

Pinar Gursoy

Keyword(s):

Lung Cancer ◽

Case Report ◽

Treatment Options ◽

Resistance Mutation ◽

Growth Factor Receptor ◽

Complete Response ◽

Egfr Mutations ◽

T790m Mutation ◽

Development Of Resistance ◽

Exon 19

Introduction Most patients with non-small-cell lung cancer tumors that have epidermal growth factor receptor (EGFR) mutations have deletion mutations in exon 19 or exon 21, or both.In recent years, targeted therapies in lung cancer have increased survival, but the development of resistance to these drugs poses a major problem. Thesubstitution of methionineforthreonine at position 790 (T790M) mutation,is primarily responsible for this resistance. However, after osimertinib used in T790M positivepatients treatment options are generally limited to chemotherapy. Case report We reported the efficacy of erlotinib, which we reapplied due to the disappearance of the resistance mutation after osimertinib in a 68-year-old patient using osimertinib after erlotinib. Management and outcome: In the patient using erlotinib due to exon 19 deletion when progression was observed and T790M positivity was detected, osimertinib treatment was initiated. However, when T790M was found to be negative with rebiopsy in progression after osimertinib, a complete response was achieved by restarting erlotinib. Discussion The strategy of restarting erlotinib treatment with negative T790M mutation detected in biopsies of patients with osimertinib resistance may be an acceptable treatment option.

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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

Oncology Letters ◽

10.3892/ol.2016.4409 ◽

2016 ◽

Vol 11 (5) ◽

pp. 3546-3550 ◽

Cited By ~ 10

Author(s):

YANG YANG ◽

BIAO ZHANG ◽

RUTIAN LI ◽

BAORUI LIU ◽

LIFENG WANG

Keyword(s):

Lung Cancer ◽

Case Report ◽

Kinase Inhibitor ◽

Small Cell ◽

Egfr Mutations ◽

Review Of The Literature ◽

Small Cell Lung ◽

Egfr Tyrosine Kinase Inhibitor ◽

Inhibitor Treatment ◽

Exon 19

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Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi

Cancers ◽

10.3390/cancers11040546 ◽

2019 ◽

Vol 11 (4) ◽

pp. 546 ◽

Cited By ~ 1

Author(s):

Philipp Jansen ◽

Ioana Cosgarea ◽

Rajmohan Murali ◽

Inga Möller ◽

Antje Sucker ◽

...

Keyword(s):

Malignant Tumors ◽

Gene Mutations ◽

Diagnostic Value ◽

Clinicopathological Parameters ◽

Braf Mutations ◽

Acral Melanoma ◽

Targeted Next Generation Sequencing ◽

Melanocytic Tumors ◽

Frequent Mutations ◽

Melanoma Subtypes

Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including n = 87 (67%) BRAF, n = 24 (18%) NRAS, and one (1%) MAP2K1 mutations. BRAF mutations were almost exclusively V600E (n = 86, 99%) and primarily found in junctional and compound naevi. NRAS mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E BRAF, KIT, NF1, and TERT promoter mutations, present in acral melanoma, were not identified. Our study identifies BRAF and NRAS mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities.

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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22066 ◽

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.

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CEA levels and EGFR mutations associated with patients in nonsmokers lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18038 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18038-e18038

Author(s):

Baohui Han ◽

Yu Dong ◽

Yanwei Zhang ◽

Bo Jin

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Mutation Rate ◽

Gene Mutations ◽

High Expression ◽

Smoking History ◽

Egfr Mutations ◽

Egfr Gene ◽

Lung Cancer Patients ◽

Serum Cea

e18038 Background: Background: As the non-smoking Asian patients with adenocarcinoma of the EGFR gene tend to have higher mutation rate, and serum CEA levels in patients with lung cancer, especially adenocarcinoma, high expression in many recent years, studies have also found that serum CEA levels in EGFR-changes before and after TKI therapy efficacy and treatment are closely related. However, whether serum CEA level and EGFR gene mutations is a correlation between two biomarkers. This study attempts to explore its relevance between EGFR gene mutations and analysis of serum CEA levels in non-smoking patients with lung cancer and it’s various clinical and pathological features. Methods: 84 cases of histologically confirmed non-smoking history in newly diagnosed lung cancer patients, respectively, serum CEA levels and histological detection of EGFR gene. According to the expression level of serum CEA patients were divided into high expression and did not express two groups were compared in patients with EGFR gene mutations. Results: 58/84 cases were found with activity EGFR gene mutations, the overall mutation rate was 69.0%, serum CEA levels high expression of EGFR gene mutation was significantly higher than non-expression group (serum CEA levels were <5ng/ml, ≥ 5ng/ml <20ng/ml, ≥ 20ng/ml patients with EGFR gene mutations histology were 63.2%, 70.8%, 81.8%). Conclusions: Non-smoking lung cancer patients with serum CEA levels and EGFR gene mutations was positively correlated.

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

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20565 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20565-e20565 ◽

Cited By ~ 1

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.

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