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Cancer Genomics & Proteomics

Ourania Romanidou, Vassiliki Kotoula, George Fountzilas
Isocitrate dehydrogenases 1 and 2 (IDH1/2) are enzymes that play a major role in the Krebs cycle. Mutations in these enzymes are found in the majority of lower gliomas and secondary glioblastomas, but also in myeloid malignancies and other cancers. IDH1 and IDH2 mutations are restricted to specific arginine residues in the active site of the enzymes and are gain-of-function, i.e. they confer a neomorphic enzyme activity resulting in the accumulation of D-2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite causing profound metabolic dysregulation which, among others, results in methylator phenotypes and in defects in homologous recombination repair...
September 2018: Cancer Genomics & Proteomics
Norihisa Saeki, Akira Saito, Yuki Sugaya, Mitsuhiro Amemiya, Hiroki Sasaki
BACKGROUND/AIM: Overall survival for the high-risk group of neuroblastoma (NB) patients still remains at 40-50%, necessitating the establishment of a curable treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is an NB-susceptibility gene with a tumor-promoting activity. Previously we conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell lines and identified 3 protein-coding genes regulated by LMO1. In this study, we extended our analyses to capture microRNA genes directly or indirectly regulated by LMO1...
September 2018: Cancer Genomics & Proteomics
Te-Cheng Yueh, Yi-Wen Hung, Tzu-Ching Shih, Cheng-Nan Wu, Shou-Cheng Wang, Yi-Liang Lai, Shih-Wei Hsu, Ming-Hsien Wu, Chun-Kai Fu, Yun-Chi Wang, Tao-Wei Ke, Wen-Shin Chang, Chia-Wen Tsai, DA-Tian Bau
BACKGROUND/AIM: The genomic role of human mouse double minute 2 (MDM2) in colorectal cancer (CRC) is unclear, therefore, our study aimed to evaluate the contribution of MDM2 genotype to the risk of CRC in Taiwan. MATERIALS AND METHODS: In this case-control study, MDM2 SNP309 T to G (rs2279744) genotypes were determined and their association with CRC risk were investigated among 362 patients with CRC and 362 age- and gender-matched healthy controls in central Taiwan...
September 2018: Cancer Genomics & Proteomics
Josef Maryáš, Jakub Faktor, Lenka Čápková, Petr Müller, Petr Skládal, Pavel Bouchal
BACKGROUND/AIM: Pul-down assay is a popular in vitro method for identification of physical interactors of selected proteins. Here, for the first time, we compared three conventional variants of pull-down assay with the streptavidin-modified surface plasmon resonance (SPR) chips for the detection of PDZ and LIM domain protein 2 (PDLIM2) interaction partners. MATERIALS AND METHODS: PDLIM2 protein-protein interactions were analysed by three variants of pull-down assay on streptavidin beads using LC-MS/MS in "Sequential Window Acquisition of all Theoretical fragment ion spectra (SWATH)" mode and compared with LC-SWATH-MS/MS data from SPR chips...
September 2018: Cancer Genomics & Proteomics
Steven Lehrer, Peter H Rheinstein
BACKGROUND: One aspect of smoking and lung cancer that has not been closely examined, is that regarding genes that may predispose to tobacco dependence. Smoking and mental illness are tightly linked, apparently the result of smokers using cigarettes to self-medicate for mental problems. The gene for solute carrier family 18 member A1 (vesicular monoamine transporter; SLC18A1) is of particular interest in this regard because of its association with schizophrenia, autism and bipolar illness as well as with cancer...
September 2018: Cancer Genomics & Proteomics
Ioannis Panagopoulos, Ludmila Gorunova, Henning Leske, Pitt Niehusmann, Lene E Johannessen, Julie Staurseth, Nina Øino, Torstein R Meling, Sverre Heim, Francesca Micci, Petter Brandal
BACKGROUND: Methylation of the O6 -methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma. MATERIALS AND METHODS: Pyrosequencing analysis was used to determine the MGMT promoter methylation status in 61 meningiomas, to clarify whether it might have a predictive role. RESULTS: Only two tumors (3%) had a mean methylation frequency higher than the cut-off value of 10% for the four CpG sites examined...
September 2018: Cancer Genomics & Proteomics
Ha Vu Tran, Alexandra K Kiemer, Volkhard Helms
BACKGROUND/AIM: Genomic DNA copy number alterations (CNAs) are frequent in tumors and have been catalogued by The Cancer Genome Atlas project. Emergence of chemoresistance frequently renders drug therapies ineffective. MATERIALS AND METHODS: We analyzed how CNAs recurrently found in the genomes of TCGA patients of thirty-one tumor types affect protein targets of antineoplastic (AN) agents. RESULTS: CNA deletions more frequently affected the targets of AN agents than CNA amplifications...
September 2018: Cancer Genomics & Proteomics
Elizabeth A Mazzio, Karam F A Soliman
BACKGROUND: Malignant melanoma cells can rapidly acquire phenotypic properties making them resistant to radiation and mainline chemotherapies such as decarbonize or kinase inhibitors that target RAS-proto-oncogene independent auto-activated mitogen-activated protein kinases (MAPK)/through dual specificity mitogen-activated protein kinase (MEK). Both drug resistance and inherent transition from melanocytic nevi to malignant melanoma involve the overexpression of histone deacetylases (HDACs) and a B-Raf proto-oncogene (BRAF) mutation...
September 2018: Cancer Genomics & Proteomics
Akihide Kondo, Yuzaburo Shimizu, Satoshi Adachi, Ikuko Ogino, Mario Suzuki, Osamu Akiyama, Hajime Arai
BACKGROUND: Fusion genes driving tumourigenesis have drawn the attention of researchers and oncologists. Despite the importance of such molecular alterations, there are no comprehensive reproducible methods for detecting fusion genes. MATERIALS AND METHODS: Nineteen paediatric brain tumours of five types, namely pilocytic astrocytoma, oligodendroglioma, anaplastic astrocytoma, glioblastoma and, ganglioglioma, were examined to detect fusion genes using a pyrosequencing-based method following RNA isolation, cDNA synthesis and real-time polymerase chain reaction...
July 2018: Cancer Genomics & Proteomics
Yoon Hee Lee, Min Kyung Kim, Hee Young Moon, Gun Oh Chong, Hyun Jung Lee, Yoon Soon Lee, Ji Young Park, Chan Hyeong Lee, Moon Chang Baek, Dae Gy Hong
BACKGROUND/AIM: This study was designed to identify candidate proteins which can be used for visualization of pelvic autonomic nerve during nerve-sparing surgery. MATERIALS AND METHODS: Both soft tissue and vesical branch of the inferior hypogastric nerve from five women were collected during surgery. These 10 tissue specimens were analysed using liquid chromatography-mass spectrometry (LC-MS) and Human Protein Atlas (HPA) for protein expression. The existence of nerve fibres was confirmed using haematoxylin and eosin (H&E) and anti-S-100 staining...
July 2018: Cancer Genomics & Proteomics
Elżbieta Fiedor, Karolina Zajda, Ewa L Gregoraszczuk
BACKGROUND/AIM: A common finding in cancer cells is the overexpression of histone deacetylases (HDACs), leading to altered expression and activity of numerous proteins involved in carcinogenesis. Considering that leptin can modulate the levels of HDACs, we hypothesised that leptin receptor antagonists can alter HDAC expression. MATERIALS AND METHODS: HDAC expression in cells exposed to leptin and leptin receptor antagonists (SHLA and Lan2) were evaluated in ovarian epithelial (OVCAR-3, CaOV3) and folliculoma (COV434, KGN) cells...
July 2018: Cancer Genomics & Proteomics
Petr Karasek, Natalia Gablo, Jan Hlavsa, Igor Kiss, Petra Vychytilova-Faltejskova, Marketa Hermanova, Zdenek Kala, Ondrej Slaby, Vladimir Prochazka
Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290...
July 2018: Cancer Genomics & Proteomics
Dai Shimizu, Tomoko Saito, Shuhei Ito, Takaaki Masuda, Junji Kurashige, Yosuke Kuroda, Hidetoshi Eguchi, Yasuhiro Kodera, Koshi Mimori
BACKGROUND: Peritoneal dissemination (PD) is one of the most common causes of cancer-related mortality in gastric cancer (GC). We aimed to identify PD-associated genes and investigate their role in GC. MATERIALS AND METHODS: We identified FGFR1 as a putative PD-associated gene using a bioinformatics approach. The biological significance of FGFR1 in epithelial-to-mesenchymal transition (EMT) was evaluated according to the correlation with genes that participated in EMT and FGFR1 knockdown experiments...
July 2018: Cancer Genomics & Proteomics
Mario Menschikowski, Carsten Jandeck, Markus Friedemann, Susan Richter, Dana Thiem, Björn Sönke Lange, Meinolf Suttorp
BACKGROUND/AIM: DNA methylation plays an important role in the initiation and propagation of carcinogenesis; however, the role of heterogeneously methylated epialleles is currently not well studied, also due to the lack of sensitive, unbiased and high throughput methods. Here, a newly developed droplet digital PCR (ddPCR)-based method was evaluated regarding its ability to quantify such heterogeneously methylated epialleles with sufficient analytical sensitivity and specificity. MATERIALS AND METHODS: Genomic DNA from blood leukocytes and bone marrow aspirate of an 8-year old male with B-cell acute lymphoblastic leukemia (B-ALL) and from normal and malignant prostate cell lines were analysed using ddPCR...
July 2018: Cancer Genomics & Proteomics
Jinyoung Jeon, Lee-So Maeng, Yoon Jin Bae, Eui-Jin Lee, Young Chul Yoon, Nara Yoon
BACKGROUND/AIM: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a very rare type of tumor, comprising these two different components in a single mass. Although several studies have determined the genetic characteristics of cHCC-CC, next-generation sequencing (NGS) data for comparing clonality of cHCC-CC are currently unavailable. MATERIALS AND METHODS: Four cHCC-CC cases were selected and HCC, CC and normal components from each case were separately micro-dissected...
July 2018: Cancer Genomics & Proteomics
Oh Kwang Kwon, Ju Mi Jeon, Eunji Sung, Ann-Yea Na, Sun Joo Kim, Sangkyu Lee
BACKGROUND: Secreted proteins play an important role in promoting cancer (PCa) cell migration and invasion. Proteogenomics helps elucidate the mechanism of diseases, discover therapeutic targets, and generate biomarkers for diagnosis through protein variations. MATERIALS AND METHODS: We carried out mass a spectrometry-based proteomic analysis of the conditioned media (CM) from two human prostate cancer cell lines, belonging to different metastatic sites, to identify potential metastatic and/or aggressive factors...
July 2018: Cancer Genomics & Proteomics
Steven Lehrer, Peter H Rheinstein, Kenneth E Rosenzweig
BACKGROUND/AIM: Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system. The serum and glucocorticoid-regulated kinase SGK1 gene is required for the growth and survival of GBM stem-like cells under both normoxic and hypoxic conditions. It has been reported that oxygenation significantly affects cellular genetic expression; 30% of the genes required in hypoxia were not required under normoxic conditions. Therefore, we examined SGK1 expression to determine if it may be a novel potential drug target for GBM...
July 2018: Cancer Genomics & Proteomics
Dayana Reverón, Christian López, Sylvia Gutiérrez, Zena E Sayegh, Teresita Antonia, Julie Dutil, Mokenge Malafa, Domenico Coppola
BACKGROUND/AIM: Microsatellite instability (MSI) results from genetic alterations involving the mismatch repair (MMR) genes MLH1, PSM2, MSH2, and MSH6. MSI has been implicated in both sporadic CRC and Lynch syndrome. The aim of the study was to assess the frequency of alterations in MMR protein expression in both primary colorectal cancer and precursor lesions among Puerto Rican patients. PATIENTS AND METHODS: A retrospective study of 84 Puerto Rican patients was performed to assess the frequency of MMR protein expression alterations in both primary CRC and precursor lesions using tissue microarray and immunohistochemistry...
July 2018: Cancer Genomics & Proteomics
Elizabeth A Mazzio, Charles A Lewis, Rashid Elhag, Karam F Soliman
Sepantronium bromide (YM-155) is believed to elicit apoptosis and mitotic arrest in tumor cells by reducing (BIRC5, survivin) mRNA. In this study, we monitored changes in survivin mRNA and protein after treating MDA-MB-231 cells with YM-155 concurrent with evaluation of whole transcriptomic (WT) mRNA and long intergenic non-coding RNA at 2 time points: 8 h sub-lethal (83 ng/mL) and 20 h at the LC50 (14.6 ng/mL). The data show a tight association between cell death and the precipitating loss of survivin protein and mRNA (-2...
July 2018: Cancer Genomics & Proteomics
Dipanjan Basu, Cláudia M Salgado, Bruce Bauer, Yasmin Khakoo, Janki R Patel, Ryan M Hoehl, Dominique M Bertolini, Joie Zabec, Morgan R Brzozowski, Miguel Reyes-Múgica
BACKGROUND: Omipalisib has been found to affect the viability of cancer cells. However, its effect on clonogenicity - a feature of cancer stem cells, is not clear. Cells isolated from neurocutaneous melanocytosis (NCM) patients' lesions grow clonogenically. The aim of this study was to investigate the effect of omipalisib treatment on clonogenic growth of NCM cells in vitro. MATERIALS AND METHODS: Clonogenic growth efficiency was evaluated by colony formation assays with or without specific growth factors...
July 2018: Cancer Genomics & Proteomics
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