Next generation sequencing AND lung cancer

INTRODUCTION: Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been developed for the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged non-small cell lung cancer (NSCLC), with the newer generation agents brigatinib, alectinib and lorlatinib showing prolonged responses. With the increasing number of target therapies available, the optimal sequence is yet to be defined, as resistance profiles may evolve over time and in response to sequential ALK inhibitors...

INTRODUCTION: Lung cancer is the second most common cancer; however, synchronous lung cancer is rare and challenging to treat. CASE PRESENTATION: We report the case of an 80-year-old female patient who presented with two lung lesions with primary tumor characteristics, which revealed squamous cell carcinoma and synchronous adenocarcinoma after histological sampling. Next-generation sequencing (NGS) analysis revealed a MET Exon 14 skipping mutation in squamous cell carcinoma and an epidermal growth factor receptor mutation in adenocarcinoma...

BACKGROUND: The molecular diagnostic and therapeutic pathway of Non-Small Cell Lung Cancer (NSCLC) stands as a successful example of precision medicine. The scarcity of material and the increasing number of biomarkers to be tested have prompted the routine application of next-generation-sequencing (NGS) techniques. Despite its undeniable advantages, NGS involves high costs that may impede its broad adoption in laboratories. This study aims to assess the detailed costs linked to the integration of NGS diagnostics in NSCLC to comprehend their financial impact...

Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, BRAF inhibitor dabrafenib, and MEK inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired BRAF V600E and EGFR mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients...

Lung cancer is a global health challenge, hindered by delayed diagnosis and the disease's complex molecular landscape. Accurate patient survival prediction is critical, motivating the exploration of various -omics datasets using machine learning methods. Leveraging multi-omics data, this study seeks to enhance the accuracy of survival prediction by proposing new feature extraction techniques combined with unbiased feature selection. Two lung adenocarcinoma multi-omics datasets, originating from the TCGA and CPTAC-3 projects, were employed for this purpose, emphasizing gene expression, methylation, and mutations as the most relevant data sources that provide features for the survival prediction models...

Uncommon (ucEGFRmuts) and rare epidermal growth factor receptor ( EGFR ) mutations account for 10-15% of diagnosed cases and consist of a heterogeneous group represented by several clusters within exons 18-21 (e.g., exon 18 point mutations, exon 21 L861X, exon 20 S768I), as well as exon 20 insertions (Ex20ins). Their incidence is under molecular and clinical investigation following recent findings that reported an increase of sensitivity and specificity of next-generation sequencing (NGS) methods. Consequently, their detection allows for the selection of emerging treatment options to significantly improve patients' outcomes in these particular subgroups of EGFR -mutated advanced non-small cell lung cancer (NSCLC)...

Lung cancer is a paradigm for a genetically driven tumor. A variety of drugs were developed targeting specific biomarkers requiring testing for tumor genetic alterations in relevant biomarkers. Different next-generation sequencing technologies are available for library generation: 1) anchored multiplex-, 2) amplicon based- and 3) hybrid capture-based-PCR. Anchored multiplex PCR-based sequencing was investigated for routine molecular testing within the national Network Genomic Medicine Lung Cancer (nNGM). Four centers applied the anchored multiplex ArcherDX-Variantplex nNGMv2 panel to re-analyze samples pre-tested during routine diagnostics...

The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years...

PURPOSE: The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with EGFR mutations. METHODS: Eligible patients had EGFR mutations (T790M or rare activating) and received osimertinib 80 mg once daily...

The heterogeneous relationship between protein expression, amplification, and mutations in human epidermal growth factor receptor 2 (HER2) in non-small cell lung cancer (NSCLC) and the optimal methods for detecting these alterations remain unclear. We aimed to elucidate the clinicopathological and molecular characteristics of HER2-altered NSCLC and investigate practical approaches for identifying patients who might benefit from HER2-targeted therapies. Using next-generation sequencing (NGS) data from 1,680 individuals, we searched for patients with HER2-altered NSCLCs, including amplifications and mutations...

Pulmonary atypical carcinoid (AC) is an extremely rare neuroendocrine tumor. The neurotrophic tropomyosin receptor kinase (NTRK) fusions are reported in only 0.5% of nonsmall cell lung cancer, and are more rare in AC with only one previously reported case. Currently, there is little established evidence on the optimal therapeutic strategies and prognosis for advanced cases. We present a female patient with metastatic AC after complete resection. Due to low expression of somatostatin receptor in this case, somatostatin analogs and peptide receptor radionuclide therapy were not available...

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Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components underlying NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background holds a great potential for the identification of epi-biomarkers for treatment response however, it is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin...

BACKGROUND: Since the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC. DATA SOURCES: We performed a literature search from January 2015 to October 2023 using the keywords non-small cell lung cancer , clinical practice guidelines , gene mutations , genomic assay , immune cancer therapy , circulating tumor DNA , predictive and prognostic biomarkers , and targeted therapies ...

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has established the precision oncology paradigm in lung cancer. Most patients with EGFR -mutated lung cancer respond but eventually acquire resistance. Methods: Patients exhibiting the EGFR p.T790M resistance biomarker benefit from sequenced targeted therapy with osimertinib. We hypothesized that metabolic response as detected by 18 F-FDG PET after short-course osimertinib identifies additional patients susceptible to sequenced therapy...

PURPOSE: Genetic mutation detection has become an important step in nonsmall-cell lung cancer (NSCLC) treatment because of the increasing number of drugs that target genomic rearrangements. A multiplex test that can detect multiple gene mutations prior to treatment is thus necessary. Currently, either next-generation sequencing (NGS)-based or polymerase chain reaction (PCR)-based tests are used. We evaluated the performance of the Oncomine Dx Target Test (ODxTT), an NGS-based multiplex biomarker panel test, and the AmoyDx Pan Lung Cancer PCR Panel (AmoyDx PLC panel), a real-time PCR-based multiplex biomarker panel test...

Introduction: Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in RET . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. RET SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC. Methods: The prevalence of RET SSVs was evaluated in 3,624 cases with next generation sequence reports, including 25 MTCs. Fisher exact analysis was performed to compare RET SSV frequency in cancers with/without a diagnosis of MTC...

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy...

BACKGROUND: Anaplastic lymphoma kinase ( ALK ) rearrangements have been reported as an important oncogenic driver in 5-7% non-small cell lung cancer (NSCLC) patients. Reports about the intergenic region (IGR) as an ALK fusion partner are rare. In this study, we report a novel IGR (chr2: 30,316,870)- ALK fusion in an advanced lung adenocarcinoma patient that responded effectively to crizotinib combined with pemetrexed. CASE PRESENTATION: A 68-year-old Chinese female was diagnosed with stage IV right lung adenocarcinoma (cT3N3M1c)...

A 52-year-old female patient receiving olaparib maintenance treatment was admitted to hospital with a low fever and chest tightness. A CT scan of the patient's chest showed diffuse ground glass shadow or miliary nodular shadow in the bilateral lungs. Her inflammatory biomarkers were almost normal, except the slightly elevated C-reactive protein. Moreover, lymphocytes count obviously decreased. Empirical treatment did not relieve her symptoms, while traditional testing developed negative results. The results of metagenomic next-generation sequencing (mNGS) revealed the presence of a potential pathogen, Actinomyces odontolyticus (A...