Driver and novel genes correlated with metastasis of non-small cell lung cancer: A comprehensive analysis

Although mutations of genes are crucial events in tumorigenesis and development, the association between gene mutations and lung cancer metastasis is still largely unknown. The goal of this study is to identify driver and novel genes associated with non-small cell lung cancer (NSCLC) metastasis. Candidate genes were identified using a novel comprehensive analysis, which was based on bioinformatics technology and meta-analysis. Firstly, EGFR, KRAS, ALK, TP53, BRAF and PIK3CA were identified as candidate driver genes. Further meta-analysis identified that EGFR (Pooled OR 1.33, 95% CI 1.19, 1.50; P < .001) and ALK (Pooled OR 1.52, 95% CI 1.22, 1.89; P < .001) mutations were associated with distant metastasis of NSCLC. Besides, ALK (Pooled OR 2.40, 95% CI 1.71, 3.38; P < .001) mutation was associated with lymph node metastasis of NSCLC. In addition, thirteen novel gene mutations were identified to be correlated with NSCLC metastasis, including SMARCA1, GGCX, KIF24, LRRK1, LILRA4, OR2T10, E..... READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2021.153551

Authors: Yongfeng Wu, Heng Ni, Dexin Yang, Yuequn Niu, Kelie Chen, Jinming Xu, Fang Wang, Song Tang, Yu Shi, Honghe Zhang, Jian Hu, Dajing Xia, Yihua Wu

Pre-Clinical, group4Kirk SmithJuly 10, 2021Metastasis, Mutation, SMARCA1, EDNRB

Radiomic prediction of mutation status based on MR imaging of lung cancer brain metastases

Lung cancer metastases comprise most of all brain metastases in adults and most brain metastases are diagnosed by magnetic resonance (MR) scans. The purpose of this study was to conduct an MR imaging-based radiomic analysis of brain metastatic lesions from patients with primary lung cancer to classify mutational status of the metastatic disease. We retrospectively identified lung cancer patients with brain metastases treated at our institution between 2009 and 2017 who underwent genotype testing of their primary lung cancer. Brain MR Images were used for segmentation of enhancing tumors and peritumoral edema, and for radiomic feature extraction. The most relevant radiomic features were identified and used with clinical data to train random forest classifiers to classify the mutation status. Of 110 patients in the study cohort (mean age 57.51 ± 12.32 years; M: F = 37:73), 75 had an EGFR mutation, 21 had an ALK translocation, and 15 had a KRAS mutation. One patient had both ALK transloca..... READ ARTICLE

Magnetic Resonance Imaging DOI:10.1016/j.mri.2020.03.002

Authors: Bihong T. Chen, Taihao Jin, Ningrong Ye, Isa Mambetsariev, Ebenezer Daniel, Tao Wang, Chi Wah Wong, Russell C. Rockne, Rivka Colen, Andrei

Response to Crizotinib Re-administration After Progression on Lorlatinib in a Patient With ALK-rearranged Non–small-cell Lung Cancer

Introduction: Chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene are detected in approximately 5% of non–small-cell lung cancers (NSCLCs) and function as oncogenic driver genes.1 First- and second-generation ALK-tyrosine kinase inhibitors (TKIs) were developed and showed clinical response for ALK-rearranged NSCLC.2, 3, 4 However, resistance to those ALK-TKIs almost develops, resulting in clinical relapse.5, 6 Lorlatinib is a third-generation ALK-TKI and has demonstrated significant antitumor activity against ALK-rearranged NSCLC with previous ALK-TKI resistance.7, 8 Although lorlatinib response was observed, relapse on lorlatinib ultimately developed.9, 10, 11 Mechanisms of lorlatinib resistance were reported,9, 10, 11 but remained unknown. Moreover, post-lorlatinib treatment has not been determined. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.06.021

Authors: Jun Sakakibara-Konishi, Hidenori Kitai, Yasuyuki Ikezawa, Yutaka Hatanaka, Takaaki Sasaki, Ryohei Yoshida, Shinichi Chiba, Shingo Matsumoto, Koichi Goto, Hidenori Mizugaki, Naofumi Shinagawa

Case StudyKirk SmithSeptember 1, 2019ALK-TKI, MET, Mutation, NGS, Sequential treatment

Computed Tomography Imaging Characteristics of Non–Small-Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangements: A Systematic Review and Meta-Analysis

Background: Young patients are rarely diagnosed with non-small cell lung cancer (NSCLC), and little is known about its predisposing genomic alterations and survival. Conclusions: Younger patients with NSCLC had a higher frequency of gene fusions than older patients and had a trend of worse OS. READ ARTICLE

Annals of Translational Medicine DOI:10.21037/atm.2019.03.39

Authors: Shifeng Yang, Zhengbo Song, Guoping Cheng

Relevance of Detection of Mechanisms of Resistance to ALK Inhibitors in ALK-Rearranged NSCLC in Routine Practice

Background: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown efficacy in the treatment of ALK-rearranged non–small-cell lung cancer (NSCLC), but the disease eventually progresses in all patients. In many cases, resistance to ALK TKIs arises through ALK mutations. Although clinical and biological data suggest variations in TKI efficacy according to the mechanism of resistance, ALK mutations are still rarely investigated in routine practice. Conclusion: Targeted next-generation sequencing is suitable for detecting ALK resistance mutations in ALK-rearranged NSCLC patients in routine practice. It might help select the best treatment at the time of disease progression during treatment with an ALK TKI. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.02.013

Authors: Philippe Jamme, Clotilde Descarpentries, Radj Gervais, Eric Dansin, Marie Wislez, Valérie Grégoire, Nicolas Richard, Simon Baldacci, Nathalie Rabbe, Maeva Kyheng, Zoulika Kherrouche, Fabienne Escande, Marie Christine Copin, Alexis B. Cortot