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https://www.readbyqxmd.com/read/29662194/an-egfr-ligand-promotes-egfr-mutant-but-not-kras-mutant-lung-cancer-in-vivo
#1
Koichi Tomoshige, Minzhe Guo, Tomoshi Tsuchiya, Takuya Fukazawa, Iris M Fink-Baldauf, William D Stuart, Yoshio Naomoto, Takeshi Nagayasu, Yutaka Maeda
EGFR ligands (e.g., EGF and TGFA) have been shown to be clinically associated with poor survival in lung cancer. Since TGFA itself initiates autochthonous tumors in liver, breast, and pancreas but not in the lung in transgenic mice in vivo, it would appear that an EGFR ligand may not initiate but rather promote lung cancer. However, it has not been proven in vivo whether lung cancer is promoted by an EGFR ligand. Using transgenic mouse models conditionally expressing EGFR L858R or Kras G12D with TGFA (an EGFR ligand) in lung epithelium, we determined that TGFA promoted the growth of EGFR L858R -lung tumors in airway regions but not that of Kras G12D -lung tumors...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29659668/cytology-cell-blocks-are-suitable-for-immunohistochemical-testing-for-pd-l1-in-lung-cancer
#2
H Wang, J Agulnik, G Kasymjanova, A Wang, V Cohen, D Small, C Pepe, L Sakr, P Fiset, M Auger, S Camilleri-Broet, M Alam El Din, G Chong, L van Kempen, A Spatz
Background: PD-L1 immunohistochemistry (IHC) testing is usually performed on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay. Methods: A total of 1419 consecutive cases of non-small cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both...
April 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29652780/implication-of-biomarker-mutations-for-predicting-survival-in-patients-with-metastatic-lung-cancer-to-the-spine
#3
Bryan D Choi, Ganesh M Shankar, Ahilan Sivaganesan, Laura A Van Beaver, Kevin Oh, John H Shin
STUDY DESIGN: A retrospective cohort study. OBJECTIVE: We performed a retrospective study of patients treated at our institution over the last 7 years to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine. SUMMARY OF BACKGROUND DATA: Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication...
April 12, 2018: Spine
https://www.readbyqxmd.com/read/29643917/predictive-and-prognostic-implications-of-mutation-profiling-and-microsatellite-instability-status-in-patients-with-metastatic-colorectal-carcinoma
#4
Jianhua Liu, Weiqiang Zeng, Chengzhi Huang, Junjiang Wang, Dongyang Yang, Dong Ma
To investigate whether mutation profiling and microsatellite instability (MSI) status were associated with clinicopathological features and the prognosis in metastatic colorectal cancer (mCRC), mutations in RAS (including KRAS , NRAS , and HRAS ) and BRAF were determined by Sanger sequencing. Tumor mismatch repair proteins and MSI status were examined using immunohistochemistry and polymerase chain reaction, respectively. The clinical value of these abnormalities was statistically analyzed, and prognostic value of different treatment regimens was also evaluated...
2018: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29624782/a-molecular-pathological-study-of-four-cases-of-ciliated-muconodular-papillary-tumors-of-the-lung
#5
Toshiaki Kataoka, Koji Okudela, Mai Matsumura, Hideaki Mitsui, Takehisa Suzuki, Chihiro Koike, Tomoe Sawazumi, Shigeaki Umeda, Yoko Tateishi, Shoji Yamanaka, Yoshihiro Ishikawa, Hiromasa Arai, Michihiko Tajiri, Kenichi Ohashi
Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low-grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung...
April 6, 2018: Pathology International
https://www.readbyqxmd.com/read/29621832/identifying-associations-between-somatic-mutations-and-clinicopathologic-findings-in-lung-cancer-pathology-reports
#6
Nishant Kumar, Laura J Tafe, John H Higgins, Jason D Peterson, Francise Blumental de Abreu, Sophie J Deharvengt, Gregory J Tsongalis, Christopher I Amos, Saeed Hassanpour
OBJECTIVE: We aim to build an informatics methodology capable of identifying statistically significant associations between the clinical findings of non-small cell lung cancer (NSCLC) recorded in patient pathology reports and the various clinically actionable genetic mutations identified from next-generation sequencing (NGS) of patient tumor samples. METHODS: We built an information extraction and analysis pipeline to identify the associations between clinical findings in the pathology reports of patients and corresponding genetic mutations...
February 2018: Methods of Information in Medicine
https://www.readbyqxmd.com/read/29610318/ablation-of-insulin-receptor-substrates-1-and-2-suppresses-kras-driven-lung-tumorigenesis
#7
He Xu, Min-Sik Lee, Pei-Yun Tsai, Ashley S Adler, Natasha L Curry, Saketh Challa, Elizaveta Freinkman, Daniel S Hitchcock, Kyle D Copps, Morris F White, Roderick T Bronson, Michael Marcotrigiano, Yaotang Wu, Clary B Clish, Nada Y Kalaany
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma ( KRAS ). Although KRAS direct binding to and activation of PI3K is required for KRAS -driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 ( Irs1 / Irs2 ), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29604399/brief-report-recurrently-mutated-genes-differ-between-leptomeningeal-and-solid-lung-cancer-brain-metastases
#8
Yingmei Li, Boxiang Liu, Ian David Connolly, Bina Wasunga Kakusa, Wenying Pan, Seema Nagpal, Stephen B Montgomery, Melanie Hayden Gephart
When compared to solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. LMD does not undergo surgical resection, limiting the tissue available for scientific research. Here we performed whole-exome sequencing (WES) on 8 LMD samples to identify somatic mutations and compared the results with 26 solid brain metastases. We found that TAS2R31 and PDE4DIP were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with retrospective chart review of an additional 44 NSCLC LMD patients, we discovered a surprisingly low number of KRAS mutations (n=4, 7...
March 28, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29587865/distinctive-features-of-immunostaining-and-mutational-load-in-primary-pulmonary-enteric-adenocarcinoma-implications-for-differential-diagnosis-and-immunotherapy
#9
Ming Chen, Pu Liu, Feifei Yan, Suzhen Xu, Qi Jiang, Jingying Pan, Mengye He, Peng Shen
BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is an extremely rare variant of invasive lung cancer. It is highly heterogeneous while shares some common morphologic and immunohistochemical features with usual pulmonary adenocarcinoma (PAC) and colorectal adenocarcinoma (CRAC), making the differential diagnosis difficult. At present there are only limited studies about distinctive features of primary PEAC and the results are often inconsistent. METHODS: We retrospectively analyzed total 129 primary PEACs and 50 CRACs that were published since 1991 or diagnosed in our centre...
March 27, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29587667/outcomes-of-pemetrexed-based-chemotherapies-in-her2-mutant-lung-cancers
#10
Yan Wang, Shijia Zhang, Fengying Wu, Jing Zhao, Xuefei Li, Chao Zhao, Shengxiang Ren, Caicun Zhou
BACKGROUND: HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas. METHODS: Patients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS)...
March 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29587142/developmental-history-provides-a-roadmap-for-the-emergence-of-tumor-plasticity
#11
Purushothama Rao Tata, Ryan D Chow, Srinivas Vinod Saladi, Aleksandra Tata, Arvind Konkimalla, Anne Bara, Daniel Montoro, Lida P Hariri, Angela R Shih, Mari Mino-Kenudson, Hongmei Mou, Shioko Kimura, Leif W Ellisen, Jayaraj Rajagopal
We show that the loss or gain of transcription factor programs that govern embryonic cell-fate specification is associated with a form of tumor plasticity characterized by the acquisition of alternative cell fates normally characteristic of adjacent organs. In human non-small cell lung cancers, downregulation of the lung lineage-specifying TF NKX2-1 is associated with tumors bearing features of various gut tissues. Loss of Nkx2-1 from murine alveolar, but not airway, epithelium results in conversion of lung cells to gastric-like cells...
March 26, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29575851/molecular-screening-of-small-biopsy-samples-using-next-generation-sequencing-in-korean-patients-with-advanced-non-small-cell-lung-cancer-korean-lung-cancer-consortium-klcc-13-01
#12
Bo Mi Ku, Mi Hwa Heo, Joo-Hang Kim, Byoung Chul Cho, Eun Kyung Cho, Young Joo Min, Ki Hyeong Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Tae Jung Kim, Ho Yun Lee, Hojoong Kim, Kyung-Jong Lee, Myung-Ju Ahn
Background: Non-small cell lung cancer (NSCLC) is a common type of cancer with typically poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC...
March 26, 2018: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/29568386/correlation-of-met-gene-amplification-and-tp53-mutation-with-pd-l1-expression-in-non-small-cell-lung-cancer
#13
Maher Albitar, Sucha Sudarsanam, Wanlong Ma, Shiping Jiang, Wayne Chen, Vincent Funari, Forrest Blocker, Sally Agersborg
Background: The role of MET amplification in lung cancer, particularly in relation to checkpoint inhibition and EGFR WT, has not been fully explored. In this study, we correlated PD-L1 expression with MET amplification and EGFR , KRAS , or TP53 mutation in primary lung cancer. Methods: In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for MET amplification by FISH with a MET /centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and TP53 , KRAS , and EGFR mutations were tested using next generation sequencing...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29559545/engaging-anaphase-catastrophe-mechanisms-to-eradicate-aneuploid-cancers
#14
REVIEW
Masanori Kawakami, Lisa Maria Mustachio, Xi Liu, Ethan Dmitrovsky
Cancer cells often have supernumerary centrosomes that promote genomic instability, a pathognomonic feature of cancer. During mitosis, cancer cells with supernumerary centrosomes undergo bipolar cell division by clustering centrosomes into two poles. When supernumerary centrosome clustering is antagonized, cancer cells are forced to undergo multipolar division leading to death of daughter cells. This proapoptotic pathway, called anaphase catastrophe, preferentially eliminates aneuploid cancer cells and malignant tumors in engineered mouse models...
March 20, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29555200/computational-systems-biology-analysis-of-biomarkers-in-lung-cancer-unravelling-genomic-regions-which-frequently-encode-biomarkers-enriched-pathways-and-new-candidates
#15
Ibrahim O Alanazi, Sami A AlYahya, Esmaeil Ebrahimie, Manijeh Mohammadi-Dehcheshmeh
Exponentially growing scientific knowledge in scientific publications has resulted in the emergence of a new interdisciplinary science of literature mining. In text mining, the machine reads the published literature and transfers the discovered knowledge to mathematical-like formulas. In an integrative approach in this study, we used text mining in combination with network discovery, pathway analysis, and enrichment analysis of genomic regions for better understanding of biomarkers in lung cancer. Particular attention was paid to non-coding biomarkers...
March 16, 2018: Gene
https://www.readbyqxmd.com/read/29554880/underutilization-and-disparities-in-access-to-egfr-testing-among-medicare-patients-with-lung-cancer-from-2010-2013
#16
Julie A Lynch, Brygida Berse, Merry Rabb, Paul Mosquin, Rob Chew, Suzanne L West, Nicole Coomer, Daniel Becker, John Kautter
BACKGROUND: Tumor testing for mutations in the epidermal growth factor receptor (EGFR) gene is indicated for all newly diagnosed, metastatic lung cancer patients, who may be candidates for first-line treatment with an EGFR tyrosine kinase inhibitor. Few studies have analyzed population-level testing. METHODS: We identified clinical, demographic, and regional predictors of EGFR & KRAS testing among Medicare beneficiaries with a new diagnosis of lung cancer in 2011-2013 claims...
March 20, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29545318/cost-effectiveness-of-kras-egfr-and-alk-testing-for-decision-making-in-advanced-nonsmall-cell-lung-carcinoma-the-french-ifct-predict-amm-study
#17
Sandrine Loubière, Alexandre Drezet, Michèle Beau-Faller, Denis Moro-Sibilot, Sylvie Friard, Marie Wislez, Hélène Blons, Catherine Daniel, Virginie Westeel, Anne Madroszyk, Hervé Léna, Patrick Merle, Julien Mazières, Gérard Zalcman, Roger Lacave, Martine Antoine, Franck Morin, Pascale Missy, Fabrice Barlesi, Pascal Auquier, Jacques Cadranel
ALK rearrangement and EGFR / KRAS mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC.Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, i.e. with "at least one biomarker status known" and "at least KRAS status known", in addition to "no biomarker testing" as the reference strategy...
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29541220/targeted-sequencing-reveals-distinct-pathogenic-variants-in-chinese-patients-with-lung-adenocarcinoma-brain-metastases
#18
Yanchun Ma, Kun Chen, Zhenhua Yang, Ming Guan
Lung cancer is the most common type of malignancy to metastasize to the brain, with the median survival time of patients being 6-11 months. In the present study, the aim was to compare the actionable gene mutation profiles of primary lung adenocarcinoma (LC) samples and LC brain metastasis (LCBM) samples through targeted sequencing. Next generation sequencing (NGS) of 13 formalin-fixed, paraffin-embedded LC samples and 15 LCBM samples was performed using a customized OncoAim™ cancer panel and OncoAim™ RNA fusion panel on the MiSeq platform...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29541205/monitoring-colorectal-cancer-following-surgery-using-plasma-circulating-tumor-dna
#19
Xiao Sun, Tanxiao Huang, Fangsheng Cheng, Kaibing Huang, Ming Liu, Wan He, Mingwei Li, Xiaoni Zhang, Mingyan Xu, Shifu Chen, Ligang Xia
Postoperative monitoring for patients with colorectal cancer (CRC) requires sensitive biomarkers that are associated with medical response and adjuvant therapy following surgery. Conventional tumor biomarkers [including carcinoembryonic antigen (CEA), CA19-9 and CA125] are widely used, but none of the markers provide high sensitivity or specificity. Previous studies indicated that circulating tumor DNA (ctDNA) is useful for postoperative monitoring of patients with cancer. However, the majority of previous studies involved patients with lung cancer, and therefore further studies are required which investigate patients with CRC...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29535536/response-to-crizotinib-in-a-non-small-cell-lung-cancer-patient-harboring-an-eml4-alk-fusion-with-an-atypical-ltbp1-insertion
#20
Cristina Aguado, Maria-de-Los-Llanos Gil, Zaira Yeste, Ana Giménez-Capitán, Cristina Teixidó, Niki Karachaliou, Santiago Viteri, Rafael Rosell, Miguel A Molina-Vila
Fusion of the anaplastic lymphoma receptor tyrosine kinase gene ( ALK ) with the echinoderm microtubule-associated protein 4 gene ( EML4 ) is the second most common actionable alteration in non-small-cell lung cancer, with a frequency of 5%. Here, we present a case of an EML4-ALK-positive patient with an atypical in-frame insertion from the LTBP1 gene in the canonical junction of variant 1 . The patient was a 39-year-old never-smoker female diagnosed with Stage IV lung adenocarcinoma. A core biopsy was negative for EGFR and KRAS mutations but positive for ALK immunohistochemistry and fluorescence in situ hybridization...
2018: OncoTargets and Therapy
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