Next generation sequencing AND lung cancer

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population...

Leptomeningeal metastasis (LM) is a devastating complication of advanced non-small cell lung cancer (NSCLC). Diagnosis and monitoring of LM can be challenging. Extracellular vesicles (EVs) microRNAs (miRNAs) have become a new noninvasive diagnostic biomarker. The purpose of this study was to examine the clinical value and role of EVs miRNAs in NSCLC-LM. According to next-generation sequencing (NGS), miRNAs with differential expression of EVs in serum of NSCLC patients with LM and non-LM were detected to find biological markers for the diagnosis of LM...

The discovery of epidermal growth factor receptor (EGFR) somatic mutations and the availability of tyrosine kinase inhibitors (TKIs) as targeted therapies have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC). p. G719X and p. S768I mutations, often present in the form of complex mutations, are considered rare. This study firstly reported the treatment outcome of a locally advanced unresectable NSCLC patient with a rare complex EGFR p. G719X/ p. S768I mutations who received befotertinib...

PURPOSE: Despite the generally favourable prognoses observed in patients with ALK-positive non-small cell lung cancer (NSCLC), there remains significant variability in clinical outcomes. The objective of this study is to enhance patient stratification by examining both the specific sites of gene fusion and the presence of co-occurring mutations. METHODS: We collected retrospective clinical and pathological data on ALK-positive patients with locally advanced or metastatic disease...

OBJECTIVES: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example...

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine...

Background   NFE2L2 (nuclear factor erythroid-2-related factor-2) encodes a basic leucine zipper (bZIP) transcription factor and exhibits variations in various tumor types, including lung cancer. In this study, we comprehensively investigated the impact of simultaneous mutations on the survival of NFE2L2 -mutant lung cancer patients within specific subgroups. Methods  A cohort of 1,103 lung cancer patients was analyzed using hybridization capture-based next-generation sequencing. Results  The NFE2L2 gene had alterations in 3...

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...