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https://www.readbyqxmd.com/read/28634423/tumor-ras-gene-expression-levels-are-influenced-by-the-mutational-status-of-ras-genes-and-both-upstream-and-downstream-ras-pathway-genes
#1
Robert M Stephens, Ming Yi, Bailey Kessing, Dwight V Nissley, Frank McCormick
The 3 human RAS genes play pivotal roles regulating proliferation, differentiation, and survival in normal cells and become mutated in 15% to 20% of all human tumors and amplified in many others. In this report, we examined data from The Cancer Genome Atlas to investigate the relationship between RAS gene mutational status and messenger RNA expression. We show that all 3 RAS genes exhibit increased expression when they are mutated in a context-dependent manner. In the case of KRAS, this increase is manifested by a larger proportional increase in KRAS4A than KRAS4B, although both increase significantly...
2017: Cancer Informatics
https://www.readbyqxmd.com/read/28634282/genomic-alterations-in-fatal-forms-of-non-anaplastic-thyroid-cancer-identification-of-med12-and-rbm10-as-novel-thyroid-cancer-genes-associated-with-tumor-virulence
#2
Tihana Ibrahimpasic, Bin Xu, Iñigo Landa, Snjezana Dogan, Sumit Middha, Venkatraman Seshan, Shyamprasad Deraje Vasudeva, Diane Carlson, Jocelyn Migliacci, Jeffrey A Knauf, Brian R Untch, Michael F Berger, Luc Gt Morris, R Michael Tuttle, Timothy A Chan, James A Fagin, Ronald Ghossein, Ian Ganly
Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. <p>Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC)...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634199/characterising-cis-regulatory-variation-in-the-transcriptome-of-histologically-normal-and-tumour-derived-pancreatic-tissues
#3
Mingfeng Zhang, Soren Lykke-Andersen, Bin Zhu, Wenming Xiao, Jason W Hoskins, Xijun Zhang, Lauren M Rost, Irene Collins, Martijn van de Bunt, Jinping Jia, Hemang Parikh, Tongwu Zhang, Lei Song, Ashley Jermusyk, Charles C Chung, Bin Zhu, Weiyin Zhou, Gail L Matters, Robert C Kurtz, Meredith Yeager, Torben Heick Jensen, Kevin M Brown, Halit Ongen, William R Bamlet, Bradley A Murray, Mark I McCarthy, Stephen J Chanock, Nilanjan Chatterjee, Brian M Wolpin, Jill P Smith, Sara H Olson, Gloria M Petersen, Jianxin Shi, Laufey Amundadottir
OBJECTIVE: To elucidate the genetic architecture of gene expression in pancreatic tissues. DESIGN: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. RESULTS: We identified 38 615 cis-eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis-eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0...
June 20, 2017: Gut
https://www.readbyqxmd.com/read/28631558/the-overexpression-and-prognostic-role-of-dcaf13-in-hepatocellular-carcinoma
#4
Jianzhong Cao, Pengjiao Hou, Jiemin Chen, Penghui Wang, Wenqin Wang, Wei Liu, Changzheng Liu, Xiaodong He
DDB1 and CUL4 associated factor 13 (DCAF13) is a protein coding gene located on chromosome 8q22.3, which is a hotspot amplified in various cancers. DCAF13 has been reported to be frequently amplified in breast cancer patients. However, the genetic alteration and potential role of DCAF13 in other cancers, including hepatocellular carcinoma, have not been investigated yet. In this study, we found that DCAF13 was amplified in 14.7% of the cases and its expression was upregulated (p < 0.001) in hepatocellular carcinoma samples in The Cancer Genome Atlas dataset...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631555/grik3-a-novel-oncogenic-protein-related-to-tumor-tnm-stage-lymph-node-metastasis-and-poor-prognosis-of-gc
#5
Baocheng Gong, Yuan Li, Zhenguo Cheng, Pengliang Wang, Lei Luo, Hanwei Huang, Shijie Duan, Funan Liu
Glutamate receptor, ionotropic, kainate 3 (GRIK3), as a member of the glutamate kainate receptor family, mainly participated in neuroactive ligand receptor interaction pathway. Other members of GRIK family were previously reported to regulate cellular migration, transformation, and proliferation in tumor. However, the mechanism of GRIK3 in tumor is still unclear. Therefore, the purpose of our study was to reveal the expression and clinical significance of GRIK3 in gastric cancer (GC). First, we performed the expression analysis and survival analysis of GRIK3 using The Cancer Genome Atlas (TCGA) database, and the results showed that the GRIK3 expressed differentially between gastric cancer tissues and the adjacent normal tissues and that higher expression of GRIK3 was associated with poor survival outcomes...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631396/pttg3p-promotes-gastric-tumour-cell-proliferation-and-invasion-and-is-an-indicator-of-poor-prognosis
#6
Weiwei Weng, Shujuan Ni, Yiqin Wang, Midie Xu, Qiongyan Zhang, Yusi Yang, Yong Wu, Qinghua Xu, Peng Qi, Cong Tan, Dan Huang, Ping Wei, Zhaohui Huang, Yuqing Ma, Wei Zhang, Weiqi Sheng, Xiang Du
Pseudogenes play a crucial role in cancer progression. However, the role of pituitary tumour-transforming 3, pseudogene (PTTG3P) in gastric cancer (GC) remains unknown. Here, we showed that PTTG3P expression was abnormally up-regulated in GC tissues compared with that in normal tissues both in our 198 cases of clinical samples and the cohort from The Cancer Genome Atlas (TCGA) database. High PTTG3P expression was correlated with increased tumour size and enhanced tumour invasiveness and served as an independent negative prognostic predictor...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#7
Jason Roszik, Wei-Lien Wang, John A Livingston, Christina L Roland, Vinod Ravi, Cassian Yee, Patrick Hwu, Andrew Futreal, Alexander J Lazar, Shreyaskumar R Patel, Anthony P Conley
BACKGROUND: PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma. METHODS: To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28628113/microrna-20a-mediated-loss-of-autophagy-contributes-to-breast-tumorigenesis-by-promoting-genomic-damage-and-instability
#8
L Liu, J He, X Wei, G Wan, Y Lao, W Xu, Z Li, H Hu, Z Hu, X Luo, J Wu, W Xie, Y Zhang, N Xu
Gene expression analysis of The Cancer Genome Atlas (TCGA) breast cancer data set show that miR-20a is upregulated in human breast cancer, especially in triple-negative subtype. Gene Set Enrichment Analysis suggests that miR-20a expression negatively correlates with the autophagy/lysosome pathway. We report here that miR-20a inhibits the basal and nutrient starvation-induced autophagic flux and lysosomal proteolytic activity, increases intracellular reactive oxygen species levels and DNA damage response by targeting several key regulators of autophagy, including BECN1, ATG16L1 and SQSTM1...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28627585/role-of-metadherin-in-estrogen-regulated-gene-expression
#9
Yujun Li, Jesus Gonzalez Bosquet, Shujie Yang, Kristina W Thiel, Yuping Zhang, Haitao Liu, Kimberly K Leslie, Xiangbing Meng
The disruption of estrogen signaling is widely associated with the development of breast, endometrial and ovarian cancers. As a multifunctional mediator of carcinogenesis, metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) overexpression has been associated with numerous types of cancer, with reported roles in tumor initiation, proliferation, invasion, metastasis and chemoresistance. At the molecular level, MTDH has been shown to interact with proteins that drive tumorigenesis, including nuclear factor-κB (NF-κB), promyelocytic leukaemia zinc finger (PLZF), BRCA2- and CDKN1A (p21Cip1/Waf-1/mda-6)-interacting protein α (BCCIPα) and staphylococcal nuclease and tudor domain containing 1 (SND1)...
June 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28625101/a-versatile-method-for-bladder-segmentation-in-computed-tomography-two-dimensional-images-under-adverse-conditions
#10
João Ribeiro Pinto, João Manuel Rs Tavares
This article presents the design and evaluation of an algorithm for urinary bladder segmentation in medical images, from contrastless computed tomography studies of patients suffering from bladder wall tumours. These situations require versatile methods of segmentation, able to adapt to the structural changes the tumours provoke in the bladder wall, reflected as irregularities on the images obtained, creating adversities to the segmentation process. This semi-automatic method uses fuzzy c-means clustering, a Gaussian-curve-based intensity transformation, and active contour models, requiring only the physician's input of a single seed point for each anatomical view, in order to segment the bladder volume in all frames that include it...
June 1, 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#11
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#12
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28619980/pan-cancer-analysis-pinpoints-targets-in-pi3k-pathway
#13
(no author information available yet)
A new study of all 32 cancer types in The Cancer Genome Atlas identifies genomic alterations that increase the activity of the PI3K/AKT/mTOR pathway. The study, which combines mutation data with measures of protein levels and phosphorylation status, suggests that mutations in IDH1, VHL, and STK11 promote activation of the pathway and may point to new drug targets.
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28618399/rna-sequencing-investigation-identifies-an-effective-risk-score-generated-by-three-novel-lncrnas-for-the-survival-of-papillary-thyroid-cancer-patients
#14
Yi-Huan Luo, Liang Liang, Rong-Quan He, Dong-Yue Wen, Guo-Fei Deng, Hong Yang, Yun He, Wei Ma, Xiao-Yong Cai, Jun-Qiang Chen, Gang Chen
Scholars are striving to apply molecular biology involving long non-coding RNA (lncRNA) in the prognostication of papillary thyroid cancer (PTC). However, the clinical role of lncRNAs in the prognostic setting of PTC is still unclear. Herein, a comprehensive inquiry was performed to screen lncRNA expression profiling with 507 PTC patients from The Cancer Genome Atlas RNA-sequencing datasets. A total of 734 lncRNAs were detected to be aberrantly expressed, among which three novel lncRNAs including AC079630.2, CRNDE and CTD-2171N6...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617833/clinical-performance-validation-of-pitx2-dna-methylation-as-prognostic-biomarker-in-patients-with-head-and-neck-squamous-cell-carcinoma
#15
Verena Sailer, Heidrun Gevensleben, Joern Dietrich, Diane Goltz, Glen Kristiansen, Friedrich Bootz, Dimo Dietrich
BACKGROUND: Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc...
2017: PloS One
https://www.readbyqxmd.com/read/28616363/insights-from-global-analyses-of-long-noncoding-rnas-in-breast-cancer
#16
Andrew J Warburton, David N Boone
PURPOSE OF REVIEW: The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of lncRNAs in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer? RECENT FINDINGS: Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousands of long noncoding RNAs that are expressed and dysregulated in breast cancer...
March 2017: Current Pathobiology Reports
https://www.readbyqxmd.com/read/28615526/identifying-prognostic-signature-in-ovarian-cancer-using-dirgenerank
#17
Jian-Yong Wang, Ling-Ling Chen, Xiong-Hui Zhou
Identifying the prognostic genes in cancer is essential not only for the treatment of cancer patients, but also for drug discovery. However, it's still a big challenge to select the prognostic genes that can distinguish the risk of cancer patients across various data sets because of tumor heterogeneity. In this situation, the selected genes whose expression levels are statistically related to prognostic risks may be passengers. In this paper, based on gene expression data and prognostic data of ovarian cancer patients, we used conditional mutual information to construct gene dependency network in which the nodes (genes) with more out-degrees have more chances to be the modulators of cancer prognosis...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615518/estrogen-activated-mdm2-disrupts-mammary-tissue-architecture-through-a-p53-independent-pathway
#18
Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiao, Chong Gao, Jill Bargonetti
The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wild-type p53 (ie, p53-independently)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614790/genomic-landscape-and-evolution-of-metastatic-chromophobe-renal-cell-carcinoma
#19
Jozefina Casuscelli, Nils Weinhold, Gunes Gundem, Lu Wang, Emily C Zabor, Esther Drill, Patricia I Wang, Gouri J Nanjangud, Almedina Redzematovic, Amrita M Nargund, Brandon J Manley, Maria E Arcila, Nicholas M Donin, John C Cheville, R Houston Thompson, Allan J Pantuck, Paul Russo, Emily H Cheng, William Lee, Satish K Tickoo, Irina Ostrovnaya, Chad J Creighton, Elli Papaemmanuil, Venkatraman E Seshan, A Ari Hakimi, James J Hsieh
Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) and ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal losses can generate proteotoxic stress and compromise cellular proliferation, it is intriguing how chRCC, a tumor with extensive chromosome losses and a low number of somatic mutations, can develop lethal metastases. Genomic features distinguishing metastatic from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS), targeted ultradeep cancer gene sequencing, and chromosome analyses (FACETS, OncoScan, and FISH), was performed on 79 chRCC patients including 38 metastatic (M-chRCC) cases...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28611308/an-oral-keratinocyte-life-cycle-model-identifies-novel-host-genome-regulation-by-human-papillomavirus-16-relevant-to-hpv-positive-head-and-neck-cancer
#20
Michael R Evans, Claire D James, Oonagh Loughran, Tara J Nulton, Xu Wang, Molly L Bristol, Brad Windle, Iain M Morgan
Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized "normal" oral keratinocytes (NOKs) we generated clonal cell lines maintaining the HPV16 genome as an episome, NOKs+HPV16...
June 1, 2017: Oncotarget
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