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https://www.readbyqxmd.com/read/28320200/clinical-and-biological-features-of-interval-colorectal-cancer
#1
Yu Mi Lee, Kyu Chan Huh
Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the "mean sojourn time." It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs...
March 21, 2017: Clinical Endoscopy
https://www.readbyqxmd.com/read/28319896/a-dynamic-sandwich-assay-on-magnetic-beads-for-selective-detection-of-single-nucleotide-mutations-at-room-temperature
#2
Junxiu Wang, Guoliang Xiong, Liang Ma, Shihui Wang, Xu Zhou, Lei Wang, Lehui Xiao, Xin Su, Changyuan Yu
Single-nucleotide mutation (SNM) has proven to be associated with a variety of human diseases. Development of reliable methods for the detection of SNM is crucial for molecular diagnosis and personalized medicine. The sandwich assays are widely used tools for detecting nucleic acid biomarkers due to their low cost and rapid signaling. However, the poor hybridization specificity of signal probe at room temperature hampers the discrimination of mutant and wild type. Here, we demonstrate a dynamic sandwich assay on magnetic beads for SNM detection based on the transient binding between signal probe and target...
March 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28319171/a-reported-20-gene-expression-signature-to-predict-lymph-node-positive-disease-at-radical-cystectomy-for-muscle-invasive-bladder-cancer-is-clinically-not-applicable
#3
Kim E M van Kessel, Harmen J G van de Werken, Irene Lurkin, Angelique C J Ziel-van der Made, Ellen C Zwarthoff, Joost L Boormans
BACKGROUND: Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) provides a small but significant survival benefit. Nevertheless, controversies on applying NAC remain because the limited benefit must be weight against chemotherapy-related toxicity and the delay of definitive local treatment. Therefore, there is a clear clinical need for tools to guide treatment decisions on NAC in MIBC. Here, we aimed to validate a previously reported 20-gene expression signature that predicted lymph node-positive disease at radical cystectomy in clinically node-negative MIBC patients, which would be a justification for upfront chemotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#4
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28319063/compromised-brca1-palb2-interaction-is-associated-with-breast-cancer-risk
#5
T K Foo, M Tischkowitz, S Simhadri, T Boshari, N Zayed, K A Burke, S H Berman, P Blecua, N Riaz, Y Huo, Y C Ding, S L Neuhausen, B Weigelt, J S Reis-Filho, W D Foulkes, B Xia
The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319062/ctcf-genetic-alterations-in-endometrial-carcinoma-are-pro-tumorigenic
#6
A D Marshall, C G Bailey, K Champ, M Vellozzi, P O'Young, C Metierre, Y Feng, A Thoeng, A M Richards, U Schmitz, M Biro, R Jayasinghe, L Ding, L Anderson, E R Mardis, J E J Rasko
CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319047/isocitrate-dehydrogenase-mutations-suppress-stat1-and-cd8-t-cell-accumulation-in-gliomas
#7
Gary Kohanbash, Diego A Carrera, Shruti Shrivastav, Brian J Ahn, Naznin Jahan, Tali Mazor, Zinal S Chheda, Kira M Downey, Payal B Watchmaker, Casey Beppler, Rolf Warta, Nduka A Amankulor, Christel Herold-Mende, Joseph F Costello, Hideho Okada
Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318385/arsenic-induced-sumoylation-of-mus81-is-involved-in-regulating-genomic-stability
#8
Liyan Hu, Feikun Yang, Lou Lu, Wei Dai
Chronic environmental exposure to metal toxicants such as chromium and arsenic is closely related to the development of several types of common cancers. Genetic and epigenetic studies in the past decade reveal that post-translational modifications of histones play a role in metal carcinogenesis. However, exact molecular mechanisms of metal carcinogenesis remain to be elucidated. In this study we found that As2O3, an environmental metal toxicant, up-regulated overall modifications of many cellular proteins by SUMO2/3...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28318368/the-wayward-methyl-group-and-the-cascade-to-cancer
#9
Robert M Hoffman
We propose here a hypothesis of the cause of cancer that brings together fundamental changes in methyl-group metabolism resulting in global DNA hypomethylation which destabilizes the genome leading to aneuploid karyotypes which evolve and stabilize into autonomous cancer. Experimental support for this hypothesis is that methioine dependence is a general metabolic defect in caner. Methionine dependence is due to excess use of methionene for aberrant transmethylation reactions that apparently divert methyl groups from DNA...
March 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28317934/dek-is-required-for-homologous-recombination-repair-of-dna-breaks
#10
Eric A Smith, Boris Gole, Nicholas A Willis, Rebeca Soria, Linda M Starnes, Eric F Krumpelbeck, Anil G Jegga, Abdullah M Ali, Haihong Guo, Amom R Meetei, Paul R Andreassen, Ferdinand Kappes, Lisa M Privette Vinnedge, Jeremy A Daniel, Ralph Scully, Lisa Wiesmüller, Susanne I Wells
DEK is a highly conserved chromatin-bound protein whose upregulation across cancer types correlates with genotoxic therapy resistance. Loss of DEK induces genome instability and sensitizes cells to DNA double strand breaks (DSBs), suggesting defects in DNA repair. While these DEK-deficiency phenotypes were thought to arise from a moderate attenuation of non-homologous end joining (NHEJ) repair, the role of DEK in DNA repair remains incompletely understood. We present new evidence demonstrating the observed decrease in NHEJ is insufficient to impact immunoglobulin class switching in DEK knockout mice...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317894/swim-a-computational-tool-to-unveiling-crucial-nodes-in-complex-biological-networks
#11
Paola Paci, Teresa Colombo, Giulia Fiscon, Aymone Gurtner, Giulio Pavesi, Lorenzo Farina
SWItchMiner (SWIM) is a wizard-like software implementation of a procedure, previously described, able to extract information contained in complex networks. Specifically, SWIM allows unearthing the existence of a new class of hubs, called "fight-club hubs", characterized by a marked negative correlation with their first nearest neighbors. Among them, a special subset of genes, called "switch genes", appears to be characterized by an unusual pattern of intra- and inter-module connections that confers them a crucial topological role, interestingly mirrored by the evidence of their clinic-biological relevance...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316978/identification-of-significant-pathways-induced-by-pax5-haploinsufficiency-based-on-protein-protein-interaction-networks-and-cluster-analysis-in-raji-cell-line
#12
Jia Gu, TongJuan Li, Lei Zhao, Xue Liang, Xing Fu, Jue Wang, Zhen Shang, Wei Huang, Jianfeng Zhou
PAX5 encodes a transcription factor essential for B-cell differentiation, and PAX5 haploinsufficiency is involved in tumorigenesis. There were few studies on how PAX5 haploinsufficiency regulated genes expression to promote tumorigenesis. In this study, we constructed the cell model of PAX5 haploinsufficiency using gene editing technology in Raji cells, detected differentially expressed genes in PAX5 haploinsufficiency Raji cells, and used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in PAX5 haploinsufficiency...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28316892/from-big-data-to-diagnosis-and-prognosis-gene-expression-signatures-in-liver-hepatocellular-carcinoma
#13
Hong Yang, Xin Zhang, Xiao-Yong Cai, Dong-Yue Wen, Zhi-Hua Ye, Liang Liang, Lu Zhang, Han-Lin Wang, Gang Chen, Zhen-Bo Feng
BACKGROUND: Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. METHODS: Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes...
2017: PeerJ
https://www.readbyqxmd.com/read/28316214/-expression-of-tyrosine-and-threonine-protein-kinase-in-carcinogenic-process-of-colorectal-cancer-and-its-relationship-with-prognosis
#14
X L Zhang, W X Han, Y M Ma, H W Y Baohan, X H Zhao, H Y Wang
Objective: To investigate the expression of TTK (tyrosine and threonine protein kinase) in the process of colorectal cancer (CRC) development and its relationship to prognosis in CRC patients. Methods: Colitis-associated colon cancer model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Mice at four different stages of colon cancer development were obtained, named AD1 (inflammation of the recovery), AD2 (mild dysplasia), AD3 (adenoma) and AD4 (adenocarcinoma), as well as negative control (no treatment)...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#15
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315701/perspective-a-defined-role-for-multiple-fanconi-anemia-gene-products-in-dna-damage-associated-ubiquitination
#16
REVIEW
Winnie Tan, Andrew J Deans
Fanconi anemia (FA) is an inherited blood disorder that causes bone marrow failure and high predisposition to cancers. The FA pathway guards the cells' genome stability by orchestrating the repair of interstrand crosslink during S phase of the cell cycle, preventing chromosomal instability that is a key event in the bone marrow failure syndrome. Central to FA pathway is loss of mono-ubiquitinated forms of the Fanconi proteins FANCI and FANCD2, a process that is normally mediated by a "core complex" of seven other Fanconi proteins...
March 15, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28315507/polymorphisms-and-mutations-in-gstp1-rad51-xrcc1-and-xrcc3-genes-in-breast-cancer-patients
#17
Mazhar Salim Al Zoubi, Katia Zavaglia, Chiara Mazanti, Mohammad Al Hamad, Khalid Al Batayneh, Alaa A A Aljabali, Generoso Bevilacqua
BACKGROUND: Genotoxic factors, including ionizing radiation and oxidative stress, are associated with genomic instability and development of breast cancer (BC). The homologous recombination DNA repair (HRR) pathway, base excision repair (BER) mechanism, and antioxidative enzymes are required as defense mechanisms against these DNA damaging agents. GSTP1, XRCC1, XRCC3 and RAD51 proteins are essential components of antioxidation, BER and HRR of DNA, respectively. Deficiencies in BER, HRR and antioxidation pathways are involved in the progression of cancer...
March 6, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28315434/identifying-the-clonal-relationship-model-of-multifocal-papillary-thyroid-carcinoma-by-whole-genome-sequencing
#18
Mao Xia, Hengyu Li, Qian Ma, Dong Yu, Jing Li, Yi Zhang, Yuan Sheng, Yingjun Guo
PURPOSE: To evaluate the application of whole genome sequencing (WGS) in determining the inter-foci clonal relationship of multifocal papillary thyroid carcinoma (mPTC). METHODS: After reviewing PTC patient profiles, 8 cancer foci and germline control samples from 3 mPTC patients were analyzed by WGS. Single nucleotide variations (SNVs), copy number variation (CNV), structural variation and mutational signature were examined. RESULTS: The multifocality rate of PTC was 35...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315227/insulin-like-growth-factor-1-gene-polymorphism-in-women-with-breast-cancer
#19
Danylo Rafhael Costa-Silva, Maria da Conceição Barros-Oliveira, Rafael Soares Borges, Larysse Maira Campos-Verdes, João Paulo da Silva-Sampaio, Carla Solange Escorcio-Dourado, Luana Mota Martins, Airlane Pereira Alencar, Edmund Chada Baracat, Vladimir Costa Silva, Benedito Borges da Silva
Breast cancer is a disease of unknown etiology; however, the major risk factors are genetic alterations. Studies have demonstrated an association between insulin-like growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two polymorphic variants of the IGF-1 gene are highlighted in association with breast cancer, rs6220 and rs7136446, although controversy exists as to this relationship. The current study included 137 women (68 breast cancer cases and 69 controls without breast cancer) who had 3 ml of peripheral blood drawn for the study of genomic DNA extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28315004/alex1-a-novel-tumor-suppressor-gene-inhibits-gastric-cancer-metastasis-via-the-par-1-rho-gtpase-signaling-pathway
#20
Li Pang, Jian-Fang Li, Liping Su, Mingde Zang, Zhiyuan Fan, Beiqin Yu, Xiongyan Wu, Chen Li, Min Yan, Zheng-Gang Zhu, Bingya Liu
BACKGROUND: The ALEX is a novel member of the armadillo family and ALEX1 was reported to be reduced or even lost in multiple solid tumors. However, its expression profile and oncogenic role in gastric cancer (GC) remains largely unknown. METHODS: ALEX1 expression was detected in 161 GC samples by immunohistochemistry staining. NCI-N87 cells transfected by ALEX1 lentivirus vectors and MKN28 cells transfected by ALEX1 shRNA were used for biological function investigation...
March 17, 2017: Journal of Gastroenterology
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