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https://www.readbyqxmd.com/read/28938622/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#1
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914263/coexistent-genetic-alterations-involving-alk-ret-ros1-or-met-in-15-cases-of-lung-adenocarcinoma
#2
Zhenya Tang, Jianjun Zhang, Xinyan Lu, Wei Wang, Hui Chen, Melissa K Robinson, Joanne Cheng, Guilin Tang, L Jeffrey Medeiros
In lung cancer, targetable activating alterations in cancer genes, such as EGFR, ALK, RET, ROS1 and MET, are usually mutually exclusive. Rare lung cancer cases with coexistent alterations of EGFR and ALK or EGFR mutations with RET or ROS1 rearrangements have been reported. In this study, we report 15 patients (3 men and 12 women; 14 Caucasians and 1 African American) with ages ranging from 43 to 81 years (median 60 years) with lung adenocarcinoma in which coexistent alterations of two cancer-associated genes, including ALK, ROS1, or RET rearrangement or MET amplification were present...
September 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#3
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28911956/alk-and-ros1-double-rearranged-lung-squamous-cell-carcinoma-responding-to-crizotinib-treatment-a-case-report
#4
Qiong Li, Jian Wu, Li-Xu Yan, Jun-Wei Huang, Zhou Zhang, Jin-E Zhang, Xing-Lin Gao, Ze-Ru Luo, Jing Liu, Shi-Fang Yang, Yan-Hui Liu
No abstract text is available yet for this article.
September 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28903995/ros1-1
#5
REVIEW
Prodipto Pal, Zanobia Khan
ROS1 is a receptor tyrosine kinase that has recently been shown to undergo gene rearrangements in~1%-2% of non-small cell lung carcinoma (NSCLC) and in a variety of other tumours including cholangiocarcinoma, gastric carcinoma, colorectal carcinoma and in spitzoid neoplasms, glioblastoma and inflammatory myofibroblastic tumours. The ROS1 gene fusion undergoes constitutive activation, regulates cellular proliferation and is implicated in carcinogenesis. ROS1 fusions can be detected by fluorescence in situ hybridisation, real-time PCR, sequencing-based techniques and immunohistochemistry-based methods in clinical laboratories...
September 13, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28903424/identification-and-characterization-of-a-novel-scyl3-ntrk1-rearrangement-in-a-colorectal-cancer-patient
#6
Massimo Milione, Elena Ardini, Jason Christiansen, Emanuele Valtorta, Silvio Veronese, Roberta Bosotti, Alessio Pellegrinelli, Adele Testi, Filippo Pietrantonio, Giovanni Fucà, Ge Wei, Danielle Murphy, Salvatore Siena, Antonella Isacchi, Filippo De Braud
In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors. Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28898463/update-on-the-potential-significance-of-psammoma-bodies-in-lung-adenocarcinoma-from-a-modern-aspect
#7
Akio Miyake, Koji Okudela, Mai Matsumura, Hideaki Mitsui, Hiromasa Arai, Shigeaki Umeda, Shoji Yamanaka, Yoshihiro Ishikawa, Michihiko Tajiri, Kenichi Ohashi
AIMS: Psammoma bodies are concentrically lamellated microscopic structures of calcium. They are commonly observed in papillary carcinomas of the thyroid gland and serous papillary adenocarcinomas of the ovary, but are also occasionally detected in lung adenocarcinomas. Only one study has ever been published in 1972, which systematically described the significance of psammoma bodies in lung adenocarcinomas. We herein updated the significance of psammoma bodies in lung adenocarcinomas from a modern aspect...
September 12, 2017: Histopathology
https://www.readbyqxmd.com/read/28894455/dna-demethylase-regulated-genes-show-methylation-independent-spatiotemporal-expression-patterns
#8
Ulrike Schumann, Joanne Lee, Kemal Kazan, Michael Ayliffe, Ming-Bo Wang
Recent research has indicated that a subset of defense-related genes is downregulated in the Arabidopsis DNA demethylase triple mutant rdd (ros1 dml2 dml3) resulting in increased susceptibility to the fungal pathogen Fusarium oxysporum. In rdd plants these downregulated genes contain hypermethylated transposable element sequences (TE) in their promoters, suggesting that this methylation represses gene expression in the mutant and that these sequences are actively demethylated in wild-type plants to maintain gene expression...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28893136/investigation-on-the-binding-mechanism-of-loratinib-with-the-c-ros-oncogene-1-ros1-receptor-tyrosine-kinase-via-molecular-dynamics-simulation-and-binding-free-energy-calculations
#9
XiaoYun Wu, YuanYuan Wang, ShanHe Wan, JiaJie Zhang
The c-ros oncogene 1 (ROS1) has proven to be an important cancer target for the treatment of various human cancers. The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been granted approval for the treatment of patients with ROS1 positive metastatic non-small-cell lung cancer (NSCLC) by the Food and Drug Administration (FDA) on 2016. However, serious resistance due to the secondary mutation of glycine 2032 to arginine (G2032R) was developed in clinical studies. Loratinib (PF-06463922), a macrocyclic analogue of crizotinib, showed significantly improved inhibitory activity against wild-type (WT) ROS1 and ROS1(G2032R) mutant...
September 11, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28888985/a-point-mutation-in-the-heavy-chain-complementarity-determining-region-3-hcdr3-significantly-enhances-the-specificity-of-an-anti-ros1-antibody
#10
Hwa Kyoung Lee, Junyeong Jin, Sang Il Kim, Min Jueng Kang, Eugene C Yi, Ji Eun Kim, Jong Bae Park, Hyori Kim, Junho Chung
The proto-oncogene tyrosine kinase ROS1 plays a key role in carcinogenesis through gene rearrangement to form a fusion protein with other genes, in which the C-terminal intracellular region of ROS1 participates. The possibility of wild type ROS1 overexpression through epigenetic regulation has been proposed. Here, we generated an antibody, 3B20, reactive to the N-terminal region of ROS1 to use it for the detection of wild type ROS1 in cancerous tissues. Using immunoblot and immunoprecipitation analyses, we found that 3B20 also reacted with heat shock proteins (Hsp)70s...
September 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28882854/mutation-of-arabidopsis-smc4-identifies-condensin-as-a-corepressor-of-pericentromeric-transposons-and-conditionally-expressed-genes
#11
Jing Wang, Todd Blevins, Ram Podicheti, Jeremy R Haag, Ek Han Tan, Feng Wang, Craig S Pikaard
In eukaryotes, transcriptionally inactive loci are enriched within highly condensed heterochromatin. In plants, as in mammals, the DNA of heterochromatin is densely methylated and wrapped by histones displaying a characteristic subset of post-translational modifications. Growing evidence indicates that these chromatin modifications are not sufficient for silencing. Instead, they are prerequisites for further assembly of higher-order chromatin structures that are refractory to transcription but not fully understood...
September 7, 2017: Genes & Development
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#12
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881815/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#13
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine. We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879708/lung-squamous-cell-carcinoma-with-de-novo-c-met-amplification
#14
Hongyang Lu, Guohua Zheng, Qi Qian
The study presented a case of lung squamous cell carcinoma (SCC) with de novo c-Met amplification. Four cycles of neoadjuvant chemotherapy were administered and partial response was achieved. Surgery was performed and the surgical margin was positive. Pathological diagnosis was lung SCC with c-ros oncogene 1 (ROS1) (+, 5%) and c-Met (++, 20%). The ROS1 rearrangement and c-Met amplification were detected using fluorescence in situ hybridization, and the result showed c-Met amplification positive and ROS1 negative...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28869223/ros1-rearrangement-and-response-to-crizotinib-in-stage-iv-non-small-cell-lung-cancer
#15
Moushumi Suryavanshi, Manoj Kumar Panigrahi, Dushyant Kumar, Haristuti Verma, Mumtaz Saifi, Bharti Dabas, Ullas Batra, Dinesh Doval, Anurag Mehta
BACKGROUND: The frequency of ROS1 rearrangement in non-small cell lung cancers has been reported from 1.6% to 2.3%. MATERIALS AND METHODS: We examined 105 lung adenocarcinoma patients for ROS1 rearrangement which were negative for EGFR and anaplastic lymphoma kinase. Clinical characteristics of ROS1 rearranged patients and their responses to crizotinib therapy were studied. RESULTS: Of the 105 patients, three cases were positive for ROS1 rearrangement by fluorescence in situ hybridization analysis...
September 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28869221/beyond-epidermal-growth-factor-receptor-egfr-and-anaplastic-lymphoma-kinase-alk-testing-in-advanced-non-small-cell-lung-cancer-is-the-picture-as-ros1-as-it-appears
#16
EDITORIAL
Navneet Singh
No abstract text is available yet for this article.
September 2017: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/28860822/response-to-crizotinib-in-a-lung-adenocarcinoma-patient-harboring-a-novel-slc34a2-ros1-fusion-variant
#17
Zheng Zhao, Zhangjun Song, Xuwei Wang, Haifeng Sun, Xiaomin Yang, Yong Yuan, Pan Yu
ROS1 fusion is a common genetic alteration in non-small-cell lung cancer. Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation. We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature. After crizotinib administration, overall recovery was good in this patient; the primary lesion was successfully treated, the lymph node metastases had disappeared, and the metabolism was normal...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28857077/fusions-in-solid-tumours-diagnostic-strategies-targeted-therapy-and-acquired-resistance
#18
REVIEW
Alison M Schram, Matthew T Chang, Philip Jonsson, Alexander Drilon
Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions...
August 31, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28845578/patient-harboring-a-novel-pik3ca-point-mutation-after-acquired-resistance-to-crizotinib-in-an-adenocarcinoma-with-ros1-rearrangement-a-case-report-and-literature-review
#19
Chun-Wei Xu, Wen-Xian Wang, Rong-Fang Huang, Cheng He, Xing-Hui Liao, You-Cai Zhu, Kai-Qi Du, Wu Zhuang, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
ROS1 rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC) cases. These patients would benefit from treatment with the anaplastic lymphoma kinase inhibitor, crizotinib; however, resistance to crizotinib inevitably develops in such patients despite an initial response. The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been identified. Herein, we report a case of a 66-year-old woman diagnosed with adenocarcinoma. PCR revealed no EGFR or ALK mutations...
August 28, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28844392/lazarus-syndrome-with-crizotinib-in-a-non-small-cell-lung-cancer-patient-with-ros1-rearrangement-and-disseminated-intravascular-coagulation
#20
Solenn Brosseau, Valérie Gounant, Charles Naltet, Nathalie Théou-Anton, Aurélie Cazes, Roland Smonig, Mathilde Neuville, Antoine Khalil, Nidaa Mikail, Véronique Meignin, Anne Bergeron, Gérard Zalcman
No abstract text is available yet for this article.
August 3, 2017: Clinical Lung Cancer
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