The Investigation of EGFR mutation and ALK gene rearrangement rates in lung adenocarcinoma patients in Mardin

Objective: Non-Small Cell Lung Cancer (NSCLC) is a heterogeneous group of tumors comprising different histologic subtypes and genetic mutations. Important mutations are EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase) rearrangement and ROS 1 rearrangement. This study aimed to determine the mutation rates of lung adenocarcinoma patients admitted to Mardin State Hospital Oncology clinic and to review the literature on the term mutually exclusivity. Materials and Methods: The records of patients admitted to Mardin State Hospital Medical Oncology Clinic between 2014-2018 were retrospectively analyzed. The descriptive statistics for continuous variables mean/median; for categorical variables, frequency (n) and percentage (%) were shown. Results: There were 39 lung adenocarcinoma patients (30.2%) among 130 lung cancer patients. The median age of female patients was 49.31 (27-74), while the median age of male patients was 58.87 (43-78). There were 6 EGFR mutant (15.4%) patients and 2 (5.1%) patients with ALK rearrangement. There were no ROS-1 positive patients. Conclusion: This study indicates that EGFR mutation rates may be very low in Turkey compared to the literature and ALK rates may be close to the literature. To determine the actual mutation rates and factors affecting genetic alterations in Turkey, there are needed to further studies.

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Analysis of Genetic Alterations in Tunisian Patients with Lung Adenocarcinoma

Cells ◽

10.3390/cells8060514 ◽

2019 ◽

Vol 8 (6) ◽

pp. 514 ◽

Cited By ~ 1

Author(s):

Dhoha Dhieb ◽

Imen Belguith ◽

Laura Capelli ◽

Elisa Chiadini ◽

Matteo Canale ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Genetic Alterations ◽

Small Sample ◽

Response To Therapy ◽

Molecular Profile ◽

Alk Rearrangement ◽

P53 Expression ◽

Anaplastic Lymphoma ◽

Tunisian Patients

The identification of the mutations that drive lung cancer have furnished new targets for the treatment of non-small cell lung cancer (NSCLC) and led to the development of targeted therapies such as tyrosine kinase inhibitors that are used to combat the molecular changes promoting cancer progression. Furthermore, biomarkers identified from gene analysis can be used to detect early lung cancer, determine patient prognosis, and monitor response to therapy. In the present study we analyzed the molecular profile of seventy-three Tunisian patients with lung adenocarcinoma (LAD). Mutational analyses for EGFR and KRAS were performed using direct sequencing, immunohistochemistry or MassARRAY. Anaplastic lymphoma kinase (ALK) rearrangement was evaluated by immunohistochemistry using the D5F3 clone, and p53 expression was also assessed. The median age of patients at diagnosis was 61 years (range 23–82 years). Using different methodologies, EGFR mutations were found in 5.47% of patients and only exon 19 deletions “E746-A750 del” were detected. KRAS mutations were present in 9.58% of cases, while only one patient was ALK-positive. Moreover, abnormal immunostaining of p53 was detected in 56.16% of patients. In conclusion, the detected rates of EGFR and KRAS mutation and ALK rearrangement were lower than those found in European and Asian countries, whereas, abnormal p53 expression was slightly more frequent. Furthermore, given the small sample size of this study, a more comprehensive analysis of this patient set is warranted.

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Two different patterns of lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement

Tumori Journal ◽

10.1177/03008916211005546 ◽

2021 ◽

pp. 030089162110055

Author(s):

Dashi Zhao ◽

Jun Fan ◽

Li Peng ◽

Bo Huang ◽

Yili Zhu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Alk Rearrangement ◽

Molecular Alterations ◽

Anaplastic Lymphoma ◽

Sporadic Cases ◽

Epidermal Growth ◽

Rare Group

Epidermal growth factor receptor ( EGFR) mutations and anaplastic lymphoma kinase ( ALK) rearrangements are considered mutually exclusive in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAC). However, sporadic cases harboring concomitant EGFR and ALK alterations have been increasingly reported. There is no consensus opinion regarding the treatment of patients positive for both molecular alterations. NSCLC with EGFR/ ALK coalterations should be separated into two subtypes: unifocal and multifocal LUAC. Here, we present an overview of the available literature regarding this rare group of patients to provide useful suggestions for therapeutic strategies.

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Reflex Testing for Epidermal Growth Factor Receptor Mutation and Anaplastic Lymphoma Kinase Fluorescence In Situ Hybridization in Non–Small Cell Lung Cancer

Archives of Pathology & Laboratory Medicine ◽

10.5858/2011-0029-rai.1 ◽

2011 ◽

Vol 135 (5) ◽

pp. 655-664

Author(s):

Mari Mino-Kenudson ◽

Eugene J. Mark

Keyword(s):

Lung Cancer ◽

Kinase Inhibitors ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Small Cell ◽

Molecular Testing ◽

Small Cell Lung ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Epidermal Growth

Abstract Context.—Non–small cell lung cancer (NSCLC) is a poor-prognosis malignancy for which more effective treatments are needed, with accumulating clinical experiences supporting benefits of receptor tyrosine kinase inhibitors for patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement. Objective.—To review completed and ongoing clinical trials of EGFR tyrosine kinase inhibitors for EGFR mutation–positive NSCLC and an ALK inhibitor for those with ALK rearrangement, while also exploring practical issues surrounding the implementation of molecular testing as a routine component of the diagnostic workup of NSCLC in the United States. Data Sources.—Published biomedical literature, abstracts presented at recent major oncology meetings, and ClinicalTrials.gov. Conclusions.—Continually evolving evidence indicates the possible efficacy of molecularly targeted agents for the treatment of advanced NSCLC, especially adenocarcinoma. To identify patients who will most likely benefit from the targeted therapy, routine determination of the corresponding genetic alterations after histologic diagnosis of NSCLC (reflex molecular testing for EGFR mutations and ALK rearrangement) should be considered.

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The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma

Pulmonary Medicine ◽

10.1155/2020/3578748 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Didik S. Heriyanto ◽

Ika Trisnawati ◽

Evan G. Kumara ◽

Vincent Laiman ◽

Fara S. Yuliani ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Fusion Gene ◽

Small Cell Lung Carcinoma ◽

Alk Rearrangement ◽

Cell Lung Carcinoma ◽

Direct Smear ◽

Nccn Guidelines ◽

Anaplastic Lymphoma ◽

Qrt Pcr

Background. Under the National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung carcinoma (NSCLC), anaplastic lymphoma kinase (ALK) gene rearrangement is required to be assessed. However, data showing the prevalence of the ALK rearrangement is still deficient and is not yet available in Indonesia. This study used direct smear preparation from transthoracic needle specimens that are minimally invasive. The main objective of the study is to identify the prevalence of the ALK fusion rearrangement gene in cytological specimens. Materials and Methods. A total of 35 direct smear preparations diagnosed as lung adenocarcinoma and EGFR mutation negative were involved in this study. The samples were taken between 2017 and 2019. These samples were examined for EML4-ALK fusion rearrangement gene using qRT-PCR. The EML4-ALK rearrangement status was determined by qRT-PCR with high-resolution melting (HRM) analysis. Results. A total of 28 (80%) samples were from males, and 7 samples were from females. Seven (20% 95% CI: 8.4%-36.9%) samples were EML4-ALK rearrangement positive. The average age of the patients was 63.5 years old. The most common sites of metastasis in this study were pleural cavity, bone, liver, and CNS. Conclusions. qRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.

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Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists

Current Respiratory Medicine Reviews ◽

10.2174/1573398x16666200319134739 ◽

2020 ◽

Vol 16 (1) ◽

pp. 5-10

Author(s):

Adrien Costantini ◽

Theodoros Katsikas ◽

Clementine Bostantzoglou

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Standard Of Care ◽

Genetic Alterations ◽

Small Cell ◽

Extensive Literature ◽

Small Cell Lung ◽

Anaplastic Lymphoma ◽

Mutational Status

Over the past decade, major breakthroughs in the understanding of lung cancer histology and mutational pathways have radically changed diagnosis and management. More specifically, in non-small cell lung cancer (NSCLC), tumour characterisation has shifted from differentiating based solely on histology to characterisation that includes genetic profiling and mutational status of Epidermal Growth Factor (EGFR), Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF. These genetic alterations can be targeted by specific drugs that result in improved progression-free survival, as well as higher response rates and are currently standard of care for NSCLC patients harbouring these mutations. In this a narrative, non-systematic review we aim to handpick through the extensive literature and critically present the ground-breaking studies that lead to the institution of tailored treatment options as the standard of care for the main targetable genetic alterations.

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EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib

BMJ Case Reports ◽

10.1136/bcr-2020-240295 ◽

2021 ◽

Vol 14 (4) ◽

pp. e240295

Author(s):

Hironari Matsuda ◽

Munechika Hara ◽

Shin-Ichiro Iwakami ◽

Kazuhisa Takahashi

Keyword(s):

Skeletal Muscle ◽

Lung Adenocarcinoma ◽

Kinase Inhibitor ◽

Stable Condition ◽

Japanese Woman ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Resistance To Treatment ◽

Alk Positive ◽

The Right

This report concerns a patient with skeletal muscle metastases due to lung adenocarcinoma harbouring an echinoderm microtubule-associated protein-like-4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement, who was successfully treated with lorlatinib after resistance to alectinib. A right lower lobectomy based on a diagnosis of lung adenocarcinoma was performed on a 77-year-old Japanese woman. After 7 months of surgical resection, a mass in the right calf was observed. A fine-needle aspiration biopsy from the mass was performed and the mass was diagnosed as metastatic adenocarcinoma harbouring EML4-ALK rearrangement. Alectinib was administered for 10 months. Then, administration of lorlatinib, an ALK tyrosine kinase inhibitor classified as third generation, was initiated after resistance to treatment with alectinib. After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.

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Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis

Scientific Reports ◽

10.1038/s41598-021-92098-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yasuto Yoneshima ◽

Eiji Iwama ◽

Shingo Matsumoto ◽

Taichi Matsubara ◽

Testuzo Tagawa ◽

...

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Lung Adenocarcinoma ◽

Genetic Alterations ◽

Driver Mutations ◽

Somatic Variant ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

And Oxidative Stress

AbstractGenetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.

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Emerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2012.45.2029 ◽

2013 ◽

Vol 31 (31) ◽

pp. 3987-3996 ◽

Cited By ~ 198

Author(s):

Justin F. Gainor ◽

Alice T. Shaw

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Genetic Alterations ◽

Anaplastic Lymphoma ◽

Development Of Resistance ◽

Tki Resistance ◽

Alk Positive ◽

Egfr Mutant

The success of tyrosine kinase inhibitors (TKIs) in select patients with non–small-cell lung cancer (NSCLC) has transformed management of the disease, placing new emphasis on understanding the molecular characteristics of tumor specimens. It is now recognized that genetic alterations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes of NSCLC that are highly responsive to genotype-directed TKIs. Despite this initial sensitivity, however, the long-term effectiveness of such therapies is universally limited by the development of resistance. Identifying the mechanisms underlying this resistance is an area of intense, ongoing investigation. In this review, we provide an overview of recent experience in the field, focusing on results from preclinical resistance models and studies of patient-derived, TKI-resistant tumor specimens. Although diverse TKI resistance mechanisms have been identified within EGFR-mutant and ALK-positive patients, we highlight common principles of resistance shared between these groups. These include the development of secondary mutations in the kinase target, gene amplification of the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant and ALK-positive patients alike, acquired resistance may also be a dynamic and multifactorial process that may necessitate the use of treatment combinations. We believe that insights into the mechanisms of TKI resistance in patients with EGFR mutations or ALK rearrangements may inform the development of novel treatment strategies in NSCLC, which may also be generalizable to other kinase-driven malignancies.

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