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tumor sequencing

Anqi Jin, Jianhao Xu, Yan Wang
BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have been described in different pathological types of thyroid cancers (TC). After many types of research focusing on the mutations rate in malignant tumors, the main role of TERT promoter mutations has been changed to the preoperative diagnosis and prognosis of TC, according to their high prevalence in aggressive TC. METHODS: We searched Pubmed, Web of Science, Scopus, and VHL and reviewed the most common 2 mutations C288T and C250T in different types of TC, the association between them and some specific clinicopathological features, and their significance in preoperative diagnosis and prognosis of TC...
July 2018: Medicine (Baltimore)
Sofie A O'Brien, Kyoungho Lee, Hsu-Yuan Fu, Zion Lee, Tung S Le, Christopher S Stach, Meghan G McCann, Alicia Q Zhang, Michael J Smanski, Nikunj V Somia, Wei-Shou Hu
For the biomanufacturing of protein biologics, establishing stable cell lines with high transgene transcription is critical for high productivity. Modern genome engineering tools can direct transgene insertion to a specified genomic locus and can potentially become a valuable tool for cell line generation. In this study, we surveyed transgene integration sites and their transcriptional activity to identify characteristics of desirable regions. A lentivirus containing destabilized Green Fluorescent Protein (dGFP) was used to infect Chinese hamster ovary cells at a low multiplicity of infection, and cells with high or low GFP fluorescence were isolated...
July 19, 2018: Biotechnology Journal
Tasia M Taxis, Marcus E Kehrli, Rui D'Orey-Branco, Eduardo Casas
Bovine leukemia virus (BLV) affects cattle health and productivity worldwide, causing abnormal immune function and immunosuppression. Transfer RNA fragments (tRFs) are known to be involved in inhibition of gene expression and have been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to identify tRFs associated with antibody response to BLV in Holstein cattle. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA. Seven animals were seropositive (positive group) and seven were seronegative (negative group) for BLV exposure...
2018: Frontiers in Genetics
Keita Maemura, Kousuke Watanabe, Takahiro Ando, Noriko Hiyama, Toshio Sakatani, Yosuke Amano, Hidenori Kage, Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Daiya Takai
Adenosine-to-Inosine (A-to-I) microRNA editing is associated with tumor phenotypes in various cancer types. Recent analyses of The Cancer Genome Atlas (TCGA) dataset have revealed several microRNAs that undergo A-to-I editing in human cancers, some of which have been reported to be associated with the prognosis. Here, we examined published small RNA deep sequencing data of 74 cases of lung adenocarcinoma (AD) and the corresponding normal counterpart (NC) specimen in silico, to identify A-to-I microRNA editing events...
July 19, 2018: Cancer Science
Xiulan Zhao, Baocun Sun, Tieju Liu, Bing Shao, Ran Sun, Dongwang Zhu, Yanhui Zhang, Qiang Gu, Xueyi Dong, Fang Liu, Nan Zhao, Danfang Zhang, Yanlei Li, Jie Meng, Wenchen Gong, Yanjun Zheng, Xu Zheng
Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with the capacity for self-renewal and multi-lineage differentiation. Previous studies have indicated that CSCs may participate in the formation of VM. With the advance of high-resolution microarrays and massively parallel sequencing technology, long non-coding RNAs (lncRNAs) are suggested to play a critical role in the tumorigenesis and, in particular, the development of human hepatocellular carcinoma (HCC)...
July 19, 2018: Cancer Science
Nam-Gu Her, Jeong-Woo Oh, Yun Jeong Oh, Suji Han, Hee Jin Cho, Yeri Lee, Gyu Ha Ryu, Do-Hyun Nam
Testing new ways to identify untapped opportunities for glioblastoma therapies remains highly significant. Amplification and overexpression of MDM2 gene is frequent in glioblastoma and disrupting the MDM2-p53 interaction is a promising strategy to treat the cancer. RG7112 is the first-in class inhibitor and recently discovered AMG232 is the most potent MDM2 inhibitor known to date. Here, we compared the effects of these two clinical MDM2 inhibitors in six glioblastoma cell lines and ten patient-derived glioblastoma stem cells...
July 18, 2018: Cell Death & Disease
Hailong Wang, Shibo Li, Joshua Oaks, Jianping Ren, Lei Li, Xiaohua Wu
Common fragile sites (CFSs) are prone to chromosomal breakage and are hotspots for chromosomal rearrangements in cancer cells. We uncovered a novel function of Fanconi anemia (FA) protein FANCM in the protection of CFSs that is independent of the FA core complex and the FANCI-FANCD2 complex. FANCM, along with its binding partners FAAP24 and MHF1/2, is recruited to CFS-derived structure-prone AT-rich sequences, where it suppresses DNA double-strand break (DSB) formation and mitotic recombination in a manner dependent on FANCM translocase activity...
July 18, 2018: Nature Communications
Nicole Panarelli, Kathrin Tyryshkin, Justin Wong, Adrianna Majewski, Xiaojing Yang, Theresa Scognamiglio, Michelle Kang Kim, Kimberley Bogardus, Thomas Tuschl, Yao-Tseng Chen, Neil Renwick
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can be challenging to evaluate histologically. microRNAs (miRNAs) are small RNA molecules that often are excellent biomarkers due to their abundance, cell-type- and disease-stage specificity, and stability. To evaluate miRNAs as adjunct tissue markers for classifying and grading well-differentiated GEP-NETs, we generated and compared miRNA expression profiles from four pathological types of GEP-NETs. Using quantitative barcoded small RNA sequencing and state-of-the-art sequence annotation, we generated comprehensive miRNA expression profiles from archived pancreatic, ileal, appendiceal, and rectal NETs...
July 18, 2018: Endocrine-related Cancer
Timon Vandamme, Matthias Beyens, Gitta Boons, Anne Schepers, Kimberly Kamp, Katharina Biermann, Patrick Pauwels, Wouter W de Herder, Leo Hofland, Marc Peeters, Guy Van Camp, Ken Op de Beeck
Mutations in DAXX/ATRX, MEN1, and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel...
July 18, 2018: Endocrine-related Cancer
Jiahui Chu, Yongfei Li, Xuemei Fan, Jingjing Ma, Jun Li, Guangping Lu, Yanhong Zhang, Yi Huang, Wei Li, Xiang Huang, Ziyi Fu, Yongmei Yin, Hongyan Yuan
BACKGROUND/AIMS: High levels of cancer stem cells (CSCs) in patients with triple-negative breast cancer (TNBC) correlate with risk of poor clinical outcome and possibly contribute to chemoresistance and metastasis in patients with highly malignant TNBC. Aberrant microRNA expression is associated with the dysfunction of self-renewal and proliferation in cancer stem cells, while there is little information about the TNBC-specific microRNAs in regulating CSC ability. METHODS: Solexa deep sequencing was performed to detect the expression levels of TNBC or non-TNBC stem cells (CSCs) microRNAs...
July 18, 2018: Cellular Physiology and Biochemistry
Chanhee Han, Gary Altwerger, Gulden Menderes, Kaitlin Haines, Jacqueline Feinberg, Salvatore Lopez, Aranzazu Manzano, Joyce Varughese, Alessandro D Santin
Carcinosarcomas (CSs) of the uterus and ovary are rare biologically aggressive tumors with poor prognosis. The development of novel, effective treatment strategies against CSs of the female genital tract remains an unmet medical need. Whole-exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in CSs including HER2, PI3K/AKT/mTOR, EGFR, MAPK, genes related to histones and chromatin structure, and genes related to cell-cycle regulation. The carcinomatous component of these biphasic tumors is suggested to be the catalyst in CS tumorigenesis...
June 2018: Discovery Medicine
(no author information available yet)
The Food and Drug Administration (FDA or we) is classifying the next generation sequencing based tumor profiling test into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the next generation sequencing based tumor profiling test's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device...
June 22, 2018: Federal Register
Nitin Udar, Catherine Lofton-Day, Jun Dong, Darcy Vavrek, A Scott Jung, Kristen Meier, Anita Iyer, Ryan Slaughter, Karen Gutekunst, Bruce A Bach, Marc Peeters, Jean-Yves Douillard
PURPOSE: To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx® sequencing instrument to simultaneously detect 56 RAS mutations in DNA extracted from formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test's ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed. METHODS: Samples from PRIME, which compared first-line panitumumab + FOLFOX4 with FOLFOX4, were processed according to predefined criteria using a multiplex assay that included input DNA qualification, library preparation, sequencing, and the bioinformatics reporting pipeline...
July 17, 2018: Journal of Cancer Research and Clinical Oncology
Xuefei Zhang, Mo Li, Desheng Lv, Ge Sun, Yu Bai, Hui Tian, Changhong Liu
BRAF mutations are known as oncogenic drivers of non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated anti-tumor activity in patients with BRAF V600E mutant NSCLC. Further molecular screening for novel BRAF thr599dup mutation is warranted. The novel BRAF Thr599dup gene mutation, for which the repeat amino acid-tyrosine is inserted between the 599th amino acid and the 600th amino acid in exon 15 of BRAF, was identified by next-generation sequencing (NGS) during routine clinical care in a lung carcinoma sample from an Asian never-smoker...
2018: Open Medicine (Warsaw, Poland)
Angana Mukherjee, Daniel P Hollern, Oluwasina G Williams, Tyeler S Rayburn, William A Byrd, Clayton Yates, Jacqueline D Jones
Development and cancer share a variety of functional traits such as EMT, cell migration, angiogenesis, and tissue remodeling. In addition, many cellular signaling pathways are noted to coordinate developmental processes and facilitate aspects of tumor progression. The Forkhead box superfamily of transcription factors consists of a highly conserved DNA binding domain, which binds to specific DNA sequences and play significant roles during adult tissue homoeostasis and embryogenesis including development, differentiation, metabolism, proliferation, apoptosis, migration, and invasion...
2018: Frontiers in Cell and Developmental Biology
Cameron Goertzen, Hayder Mahdi, Catherine Laliberte, Tomer Meirson, Denise Eymael, Hava Gil-Henn, Marco Magalhaes
Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva...
June 26, 2018: Oncotarget
Shariq S Khwaja, Chunyu Cai, Shahed N Badiyan, Xiaowei Wang, Jiayi Huang
Background: Glioblastoma (GBM) has a high rate of local recurrence despite chemoradiotherapy (CRT). Genome-wide expression profiling was performed on patient tumors before and after chemoradiotherapy to identify genes and gene pathways associated with recurrence. Results: Median time to recurrence was 8.9 months with median time to second surgery of 9.6 months. The microRNA (miRNA) analysis identified 9 oncologic and immune-related miRNAs to be differentially expressed, including the hypoxia-related miR-210 and the immune-modulatory miR-146b...
June 26, 2018: Oncotarget
Alberto Puccini, Heinz-Josef Lenz, John L Marshall, David Arguello, Derek Raghavan, W Michael Korn, Benjamin A Weinberg, Kelsey Poorman, Arielle L Heeke, Philip A Philip, Anthony F Shields, Richard M Goldberg, Mohamed E Salem
BACKGROUND: The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors in the descending colon and rectum. Therefore, we aimed to explore the molecular differences of left-sided CRC between younger (≤45 years) and older patients (≥65). SUBJECTS, MATERIALS, AND METHODS: In total, 1,126 CRC tumor samples from the splenic flexure to (and including) the rectum were examined by next-generation sequencing (NGS), immunohistochemistry, and in situ hybridization...
July 17, 2018: Oncologist
Luis Javier Galindo, Tamara Hernández-Beeftink, Ana Salas, Yaiza Jung, Ricardo Reyes, Francisco Montes de Oca, Mariano Hernández, Teresa A Almeida
OBJECTIVE: Around 70% of uterine leiomyomas show MED12 mutations while overexpression of HMGA2 mRNA is also highly frequent in fibroids. However, previous studies suggested that alterations in both genes are mutually exclusive. In the present study, we searched for mutation in MED12 and analyzed the expression of HMGA2 in 20 uterine leiomyomas and their matched myometrium. METHODS: Normal and tumor tissue obtained from premenopausal women who underwent hysterectomy were collected after surgery and DNA, RNA and proteins were isolated and analyzed for MED12 mutations using Sanger sequencing, HMGA2 mRNA expression by quantitative PCR and HMGA2 protein detection by western blot and immunohistochemistry...
July 12, 2018: Gynecologic Oncology
Kobe Reynders, Els Wauters, Matthieu Moisse, Herbert Decaluwé, Paul De Leyn, Stéphanie Peeters, Maarten Lambrecht, Kristiaan Nackaerts, Christophe Dooms, Wim Janssens, Johan Vansteenkiste, Diether Lambrechts, Dirk De Ruysscher
BACKGROUND: Gene expression of specific therapeutic targets in non-malignant lung tissue might play an important role in optimizing targeted therapies. This study aims to identify different expression patterns of fifteen genes important for targeted therapy in non-small cell lung cancer (NSCLC). METHODS: We prospectively collected tissue of NSCLC and non-malignant lung tissue from 25 primary resected patients. RNA-sequencing and 450 K methylation array profiling was applied to both NSCLC and non-malignant lung tissue and data were analyzed for 14 target genes...
July 17, 2018: Radiation Oncology
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