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https://www.readbyqxmd.com/read/28640116/distribution-of-somatic-mutations-of-cancer-related-genes-according-to-microsatellite-instability-status-in-korean-gastric-cancer
#1
Joonhong Park, Han Mo Yoo, Woori Jang, Soyoung Shin, Myungshin Kim, Yonggoo Kim, Seung-Woo Lee, Jeong Goo Kim
In studies of the molecular basis of gastric cancer (GC), microsatellite instability (MSI) is one of the key factors. Somatic mutations found in GC are expected to contribute to MSI-high (H) tumorigenesis. We estimated somatic mutation distribution according to MSI status in 52 matched pair GC samples using the Ion Torrent Ion S5 XL with the AmpliSeq Cancer Hotspot panel.Seventy-five (9.8%) somatic variants consisting of 34 hotspot mutations and 41 other likely pathogenic variants were identified in 34 GC samples...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28637868/decreased-mir26a-b-and-increased-hur-expression-post-transcriptionally-upregulates-erbb2-to-mediate-acquired-tamoxifen-resistance-in-er-breast-cancer-cells
#2
Sheng Tan, Keshuo Ding, Qing-Yun Chong, Junsong Zhao, Yuan Liu, Yunying Shao, Yuanyuan Zhang, Qing Yu, Zirui Xiong, Weijie Zhang, Min Zhang, Gaopeng Li, Xiaoni Li, Xiangjun Kong, Akhlaq Ahmad, Zhengsheng Wu, Qiang Wu, Xiaodong Zhao, Peter E Lobie, Tao Zhu
Tamoxifen-resistant ER-positive breast cancer is characterized by elevated ERBB2 expression. However, the underlying mechanisms responsible for the increased ERBB2 expression in the tamoxifen resistant (TAMR) cells remains poorly understood. Herein, we reported that the ERBB2 expression is regulated at the post-transcriptional level by miR26a/b and the RNA-binding protein HuR, both of which associate with the 3'UTR of the ERBB2 transcripts. We demonstrated that miR26a/b inhibits the translation of ERBB2 mRNA, while HuR enhances the stability of the ERBB2 mRNA...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#3
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28628842/matching-genomic-molecular-aberrations-with-molecular-targeted-agents-are-biliary-tract-cancers-an-ideal-playground
#4
REVIEW
Loic Verlingue, Antoine Hollebecque, Valérie Boige, Michel Ducreux, David Malka, Charles Ferté
Biliary tract cancers (BTCs) are a heterogeneous group of tumours with geographical discrepancies in terms of incidence and risk factors. However, a convergent genomic and epigenetic mutational landscape emerges from the genome-wide screens of BTCs in South East Asia, Latin America and in the Western World. Specificities are observed for some alterations and anatomical subtypes: frequent fibroblast growth factor receptor 2 (FGFR2) and isocitrate dehydrogenase 1/2 (IDH1/2) alterations are specific to intrahepatic cholangiocarcinomas (ICCs), whereas frequent ERBB2 oncogene alterations are specific to extrahepatic cholangiocarcinomas (ECCs) and gallbladder carcinomas (GBCs)...
June 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28626969/different-patterns-of-expression-of-cell-cycle-control-and-local-invasion-related-proteins-in-oral-squamous-cell-carcinoma-affecting-young-patients
#5
Marisol Miranda Galvis, Alan Roger Santos-Silva, Juscelino Freitas Jardim, Felipe Paiva Fonseca, Marcio A Lopes, Oslei P Almeida, Clóvis A Lópes Pinto, Estela Kaminagakura, Iris Sawazaki-Calone, Paul M Speight, Luiz Paulo Kowalski
Oral squamous cell carcinoma (OSCC) predominantly affects males in the fifth decade of life; nevertheless, an increased incidence in young patients has been reported worldwide and the clinical and behavioral characteristics of tumors in this group are controversial and the literature shows divergent results PURPOSE: To investigate the clinicopathological features and prognostic significance of the immunoexpression of cell cycle and local invasion proteins in OSCC affecting young patients (≤ 40 years old) METHODS: A tissue microarray was performed with 132 OSCC samples (61 cases of young patients vs...
June 19, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28623147/neuregulin-1-protects-mouse-cerebellum-against-oxidative-stress-and-neuroinflammation
#6
Junping Xu, Chengliang Hu, Shuangxi Chen, Huifan Shen, Qiong Jiang, Peizhi Huang, Weijiang Zhao
Cerebellum undergoes degenerative changes in neurodegenerative diseases. Two main factors including oxidative stress and neuroinflammation mediate neurodegeneration. Neuregulin-1 (Nrg1) has been implicated in many neurodegenerative diseases, while the underlying mechanisms are unknown. We hypothesized that Nrg1 prevents oxidative stress and neuroinflammation in neurodegeneration. We found a positive correlation between Nrg1 protein levels and ErbB4 and ErbB2 receptor phosphorylation in microarrays of normal human cerebellar tissue...
June 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#7
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28617917/genomic-profiling-of-small-bowel-adenocarcinoma
#8
Alexa B Schrock, Craig E Devoe, Robert McWilliams, James Sun, Thomas Aparicio, Philip J Stephens, Jeffrey S Ross, Richard Wilson, Vincent A Miller, Siraj M Ali, Michael J Overman
Importance: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking. Objective: To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations. Design, Setting, and Participants: Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions...
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28611940/involvement-of-chromatin-remodeling-genes-and-the-rho-gtpases-rhob-and-cdc42-in-ovarian-clear-cell-carcinoma
#9
Nicolai Skovbjerg Arildsen, Jenny-Maria Jönsson, Katarina Bartuma, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid A Hedenfalk
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28611201/relationship-of-the-breast-ductal-carcinoma-in-situ-immune-microenvironment-with-clinico-pathological-and-genetic-features
#10
Shona Hendry, Jia-Min B Pang, David Byrne, Sunil R Lakhani, Margaret C Cummings, Ian G Campbell, G Bruce Mann, Kylie L Gorringe, Stephen B Fox
The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown. <br /><br />Experimental Design: We quantified tumour associated lymphocytes (TILs) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases respectively), some of which had copy number (n=55) and mutation data (n=20). <br /><br />Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range 0-90%)...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28606923/detection-of-driver-and-resistance-mutations-in-leptomeningeal-metastases-of-nsclc-by-next-generation-sequencing-of-cerebrospinal-fluid-circulating-tumor-cells
#11
Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhihong Chen, Jian Su, Wenzhao Zhong, Xue-Ning Yang, Jinji Yang, Yang W Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chongrui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, Yi-Long Wu
<p>Leptomeningeal metastases (LM) are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of LM.</p> <br />Experimental Design: <p>We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients...
June 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599900/clinicopathologic-and-molecular-markers-in-cervical-carcinoma-a-prospective-cohort-study
#12
Mari Kyllesø Halle, Akinyemi I Ojesina, Hilde Engerud, Kathrine Woie, Ingvild Løberg Tangen, Frederik Holst, Erling Høivik, Kanthida Kusonmano, Ingfrid S Haldorsen, Olav K Vintermyr, Jone Trovik, Bjørn I Bertelsen, Helga B Salvesen, Camilla Krakstad
BACKGROUND: Cervical cancer is a major health problem worldwide. Identification of effective clinicopathologic and molecular markers is vital to improve treatment stratification. OBJECTIVES: To validate a set of well-defined clinicopathologic features in a large population based, prospectively collected cervical cancer cohort to support their use in the clinic. Further, we explore p53 and HER2 as potential prognostic markers in cervical cancer. STUDY DESIGN: Tissue was collected from 401 cervical cancer patients...
June 6, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28596815/next-generation-sequencing-traces-human-induced-pluripotent-stem-cell-lines-clonally-generated-from-heterogeneous-cancer-tissue
#13
Tetsuya Ishikawa
AIM: To investigate genotype variation among induced pluripotent stem cell (iPSC) lines that were clonally generated from heterogeneous colon cancer tissues using next-generation sequencing. METHODS: Human iPSC lines were clonally established by selecting independent single colonies expanded from heterogeneous primary cells of S-shaped colon cancer tissues by retroviral gene transfer (OCT3/4, SOX2, and KLF4). The ten iPSC lines, their starting cancer tissues, and the matched adjacent non-cancerous tissues were analyzed using next-generation sequencing and bioinformatics analysis using the human reference genome hg19...
May 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28596498/somatic-mutations-in-salivary-duct-carcinoma-and-potential-therapeutic-targets
#14
Timothy K Khoo, Bing Yu, Joel A Smith, Angus J Clarke, Peter P Luk, Christina I Selinger, Kate L Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J Boyer, Marcel E Dinger, Mark J Cowley, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
BACKGROUND: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. RESULTS: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#15
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589903/tumor-biomarker-conversion-between-primary-and-metastatic-breast-cancer-mrna-assessment-and-its-concordance-with-immunohistochemistry
#16
Stefan Stefanovic, Ralph Wirtz, Thomas M Deutsch, Andreas Hartkopf, Peter Sinn, Zsuzsanna Varga, Bettina Sobottka, Lakis Sotiris, Florin-Andrei Taran, Christoph Domschke, Andre Hennigs, Sara Y Brucker, Christof Sohn, Florian Schuetz, Andreas Schneeweiss, Markus Wallwiener
Biomarker changes between primary (PT) and metastatic tumor (MT) site may be significant in individualizing treatment strategies and can result from actual clonal evolution, biomarker conversion, or technical limitations of diagnostic tests.This study explored biomarker conversion during breast cancer (BC) progression in 67 patients with different tumor subtypes and metastatic sites via mRNA quantification and subsequently analyzed the concordance between real-time qPCR and immunohistochemistry (IHC). Immunostaining for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 was performed on formalin-fixed, paraffin-embedded PT and MT tissue sections...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586760/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#17
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28584208/establishment-of-a-novel-method-for-screening-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-mutations-in-lung-cancer
#18
Hong-Xia Tian, Xu-Chao Zhang, Zhen Wang, Jin-Ji Yang, Wei-Bang Guo, Zhi-Hong Chen, Yi-Long Wu
BACKGROUND: Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform...
June 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28583311/next-generation-sequencing-of-nonmuscle-invasive-bladder-cancer-reveals-potential-biomarkers-and-rational-therapeutic-targets
#19
Eugene J Pietzak, Aditya Bagrodia, Eugene K Cha, Esther N Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E Rosenberg, Dean F Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B Solit, Bernard H Bochner
BACKGROUND: Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. OBJECTIVE: To identify genetic alterations with potential clinical implications in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory...
June 2, 2017: European Urology
https://www.readbyqxmd.com/read/28573215/molecular-histologic-and-radiologic-findings-of-high-grade-invasive-adenocarcinoma-arising-in-oncocytic-subtype-of-intraductal-papillary-mucinous-neoplasm-a-case-report-and-review-of-literature
#20
Jared Shows, Christan Bartsch, Heather Carmichael, Irfan Qureshi, Barish Edil, Hubert Fenton
Background: We present a case of adenocarcinoma arising in the oncocytic subtype of intraductal papillary mucinous neoplasm (O-IPMN), with emphasis on the molecular findings in the adenocarcinoma component. Tissue microdissection and next-generation sequencing were performed using a 26 gene panel (AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, SRC, STK11, TP53) of cancer-related genes. Case Presentation: A 69-year-old Caucasian female presented with chest pain and was found to have findings consistent with acute pancreatitis...
2017: J Pancreat Cancer
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