137 results on '"Rust, Alistair G."'
Search Results
102. Correction: Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics
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Ramsey, Stephen A., primary, Klemm, Sandy L., additional, Zak, Daniel E., additional, Kennedy, Kathleen A., additional, Thorsson, Vesteinn, additional, Li, Bin, additional, Gilchrist, Mark, additional, Gold, Elizabeth S., additional, Johnson, Carrie D., additional, Litvak, Vladimir, additional, Navarro, Garnet, additional, Roach, Jared C., additional, Rosenberger, Carrie M., additional, Rust, Alistair G., additional, Yudkovsky, Natalya, additional, Aderem, Alan, additional, and Shmulevich, Ilya, additional
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- 2008
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103. Probabilistic Inference of Transcription Factor Binding from Multiple Data Sources
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Lähdesmäki, Harri, primary, Rust, Alistair G., additional, and Shmulevich, Ilya, additional
- Published
- 2008
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104. Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics
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Ramsey, Stephen A., primary, Klemm, Sandy L., additional, Zak, Daniel E., additional, Kennedy, Kathleen A., additional, Thorsson, Vesteinn, additional, Li, Bin, additional, Gilchrist, Mark, additional, Gold, Elizabeth S., additional, Johnson, Carrie D., additional, Litvak, Vladimir, additional, Navarro, Garnet, additional, Roach, Jared C., additional, Rosenberger, Carrie M., additional, Rust, Alistair G., additional, Yudkovsky, Natalya, additional, Aderem, Alan, additional, and Shmulevich, Ilya, additional
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- 2008
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105. The Innate Immune Database (IIDB)
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Korb, Martin, primary, Rust, Alistair G, additional, Thorsson, Vesteinn, additional, Battail, Christophe, additional, Li, Bin, additional, Hwang, Daehee, additional, Kennedy, Kathleen A, additional, Roach, Jared C, additional, Rosenberger, Carrie M, additional, Gilchrist, Mark, additional, Zak, Daniel, additional, Johnson, Carrie, additional, Marzolf, Bruz, additional, Aderem, Alan, additional, Shmulevich, Ilya, additional, and Bolouri, Hamid, additional
- Published
- 2008
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106. Erratum: Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4
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Gilchrist, Mark, primary, Thorsson, Vesteinn, additional, Li, Bin, additional, Rust, Alistair G., additional, Korb, Martin, additional, Roach, Jared C., additional, Kennedy, Kathleen, additional, Hai, Tsonwin, additional, Bolouri, Hamid, additional, and Aderem, Alan, additional
- Published
- 2008
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107. Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5+/- leukemia.
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van der Weyden, Louise, Giotopoulos, George, Kim Wong, Rust, Alistair G., Robles-Espinoza, Carla Daniela, Hikari Osaki, Huntly, Brian J., and Adams, David J.
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LYMPHOBLASTIC leukemia in children ,CANCER-related mortality ,B cells ,CHROMOSOME abnormalities ,MUTAGENESIS ,TRANSPOSONS ,DIAGNOSIS - Abstract
Background: B-cell precursor acute lymphoblastic leukemia (B-ALL) is amongst the leading causes of childhood cancer-related mortality. Its most common chromosomal aberration is the ETV6-RUNX1 fusion gene, with ~25% of ETV6-RUNX1 patients also carrying PAX5 alterations. Methods: We have recreated this mutation background by inter-crossing Etv6-RUNX1 (Etv6
RUNX1-SB ) and Pax5+/- mice and performed an in vivo analysis to find driver genes using Sleeping Beauty transposon-mediated mutagenesis and also exome sequencing. Results: Combination of Etv6-RUNX1 and Pax5+/- alleles generated a transplantable B220 + CD19+ B-ALL with a significant disease incidence. RNA-seq analysis showed a gene expression pattern consistent with arrest at the pre-B stage. Analysis of the transposon common insertion sites identified genes involved in B-cell development (Zfp423) and the JAK/STAT signaling pathway (Jak1, Stat5 and Il2rb), while exome sequencing revealed somatic hotspot mutations in Jak1 and Jak3 at residues analogous to those mutated in human leukemias, and also mutation of Trp53. Conclusions: Powerful synergies exists in our model suggesting STAT pathway activation and mutation of Trp53 are potent drivers of B-ALL in the context of Etv6-RUNX1;Pax5+/- . [ABSTRACT FROM AUTHOR]- Published
- 2015
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108. Transposon mutagenesis identifies genetic drivers of BrafV600E melanoma.
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Mann, Michael B, Copeland, Neal G, Jenkins, Nancy A, Black, Michael A, Jones, Devin J, Newberg, Justin Y, Ward, Jerrold M, Yew, Christopher Chin Kuan, Dupuy, Adam J, Rust, Alistair G, Bosenberg, Marcus W, McMahon, Martin, and Print, Cristin G
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TRANSPOSONS ,MUTAGENESIS ,MELANOGENESIS ,ONCOGENIC DNA viruses ,NETRINS - Abstract
Although nearly half of human melanomas harbor oncogenic BRAF
V600E mutations, the genetic events that cooperate with these mutations to drive melanogenesis are still largely unknown. Here we show that Sleeping Beauty (SB) transposon-mediated mutagenesis drives melanoma progression in BrafV600E mutant mice and identify 1,232 recurrently mutated candidate cancer genes (CCGs) from 70 SB-driven melanomas. CCGs are enriched in Wnt, PI3K, MAPK and netrin signaling pathway components and are more highly connected to one another than predicted by chance, indicating that SB targets cooperative genetic networks in melanoma. Human orthologs of >500 CCGs are enriched for mutations in human melanoma or showed statistically significant clinical associations between RNA abundance and survival of patients with metastatic melanoma. We also functionally validate CEP350 as a new tumor-suppressor gene in human melanoma. SB mutagenesis has thus helped to catalog the cooperative molecular mechanisms driving BRAFV600E melanoma and discover new genes with potential clinical importance in human melanoma. [ABSTRACT FROM AUTHOR]- Published
- 2015
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109. Using Feature Selection Filtering Methods for Binding Site Predictions
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Sun, Yi, primary, Robinson, Mark, additional, Adams, Rod, additional, Boekhorst, Rene te, additional, Rust, Alistair G., additional, and Davey, Neil, additional
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- 2006
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110. TRANSCRIPTION BINDING SITE PREDICTION USING MARKOV MODELS
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ABNIZOVA, IRINA, primary, RUST, ALISTAIR G., additional, ROBINSON, MARK, additional, TE BOEKHORST, RENE, additional, and GILKS, WALTER R., additional
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- 2006
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111. IMPROVING COMPUTATIONAL PREDICTIONS OF CIS-REGULATORY BINDING SITES
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ROBINSON, MARK, primary, SUN, YI, additional, BOEKHORST, RENE TE, additional, KAYE, PAUL, additional, ADAMS, ROD, additional, DAVEY, NEIL, additional, and RUST, ALISTAIR G., additional
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- 2005
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112. Evolutionary Neural Topiaryt: Growing and Sculpting Artificial Neurons to Order.
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Rust, Alistair G., Adams, Rod, and Bolouri, Hamid
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- 2000
113. Insertional Mutagenesis and Deep Profiling Reveals Gene Hierarchies and a Myc/p53-Dependent Bottleneck in Lymphomagenesis.
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Huser, Camille A., Gilroy, Kathryn L., de Ridder, Jeroen, Kilbey, Anna, Borland, Gillian, Mackay, Nancy, Jenkins, Alma, Bell, Margaret, Herzyk, Pawel, van der Weyden, Louise, Adams, David J., Rust, Alistair G., Cameron, Ewan, and Neil, James C.
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RETROVIRUS diseases ,MUTAGENESIS ,MOUSE leukemia ,TRANSGENIC mice ,CANCER invasiveness - Abstract
Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics that was combined in this study with deep sequencing (RIM/DS) to facilitate a comprehensive analysis of lymphoma progression. Transgenic mice expressing two potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid onset tumours that can be accelerated and rendered polyclonal by neonatal Moloney murine leukaemia virus (MoMLV) infection. RIM/DS analysis of 28 polyclonal lymphomas identified 771 common insertion sites (CISs) defining a ‘progression network’ that encompassed a remarkably large fraction of known MoMLV target genes, with further strong indications of oncogenic selection above the background of MoMLV integration preference. Progression driven by RIM was characterised as a Darwinian process of clonal competition engaging proliferation control networks downstream of cytokine and T-cell receptor signalling. Enhancer mode activation accounted for the most efficiently selected CIS target genes, including Ccr7 as the most prominent of a set of chemokine receptors driving paracrine growth stimulation and lymphoma dissemination. Another large target gene subset including candidate tumour suppressors was disrupted by intragenic insertions. A second RIM/DS screen comparing lymphomas of wild-type and parental transgenics showed that CD2-MYC tumours are virtually dependent on activation of Runx family genes in strong preference to other potent Myc collaborating genes (Gfi1, Notch1). Ikzf1 was identified as a novel collaborating gene for Runx2 and illustrated the interface between integration preference and oncogenic selection. Lymphoma target genes for MoMLV can be classified into (a) a small set of master regulators that confer self-renewal; overcoming p53 and other failsafe pathways and (b) a large group of progression genes that control autonomous proliferation in transformed cells. These findings provide insights into retroviral biology, human cancer genetics and the safety of vector-mediated gene therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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114. Inactivating CUX1 mutations promote tumorigenesis.
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Wong, Chi C, Martincorena, Inigo, Rust, Alistair G, Rashid, Mamunur, Alifrangis, Constantine, Alexandrov, Ludmil B, Tiffen, Jessamy C, Kober, Christina, Green, Anthony R, Massie, Charles E, Nangalia, Jyoti, Lempidaki, Stella, Döhner, Hartmut, Döhner, Konstanze, Bray, Sarah J, McDermott, Ultan, Papaemmanuil, Elli, Campbell, Peter J, and Adams, David J
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GENE silencing ,GENETIC mutation ,NEOPLASTIC cell transformation ,CANCER genetics ,HOMEOBOX proteins ,GENETIC transcription - Abstract
A major challenge in cancer genetics is to determine which low-frequency somatic mutations are drivers of tumorigenesis. Here we interrogate the genomes of 7,651 diverse human cancers and find inactivating mutations in the homeodomain transcription factor gene CUX1 (cut-like homeobox 1) in ∼1-5% of various tumors. Meta-analysis of CUX1 mutational status in 2,519 cases of myeloid malignancies reveals disruptive mutations associated with poor survival, highlighting the clinical significance of CUX1 loss. In parallel, we validate CUX1 as a bona fide tumor suppressor using mouse transposon-mediated insertional mutagenesis and Drosophila cancer models. We demonstrate that CUX1 deficiency activates phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), leading to increased tumor growth and susceptibility to PI3K-AKT inhibition. Thus, our complementary approaches identify CUX1 as a pan-driver of tumorigenesis and uncover a potential strategy for treating CUX1-mutant tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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115. Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model.
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Bard-Chapeau, Emilie A, Nguyen, Anh-Tuan, Rust, Alistair G, Sayadi, Ahmed, Lee, Philip, Chua, Belinda Q, New, Lee-Sun, de Jong, Johann, Ward, Jerrold M, Chin, Christopher K Y, Chew, Valerie, Toh, Han Chong, Abastado, Jean-Pierre, Benoukraf, Touati, Soong, Richie, Bard, Frederic A, Dupuy, Adam J, Johnson, Randy L, Radda, George K, and Chan, Eric Chun Yong
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TRANSPOSONS ,HEPATITIS B ,LABORATORY mice ,MUTAGENESIS ,LIVER cancer ,GENETIC regulation - Abstract
The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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116. Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma.
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Mann, Karen M., Ward, Jerrold M., Yew, Christopher Chin Kuan, Kovochich, Anne, Dawson, David W., Black, Michael A., Brett, Benjamin T., Sheetz, Todd E., Dupuy, Adam J., Chang, David K., Biankin, Andrew V., Waddell, Nicola, Kassahn, Karin S., Grimmond, Sean M., Rust, Alistair G., Adams, David J., Jenkins, Nancy A., and Copeland, Neal G.
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PANCREATIC cancer ,MUTAGENESIS ,ADENOCARCINOMA ,CANCER invasiveness ,CANCER genes ,GENE frequency ,CHROMATIN ,LABORATORY mice - Abstract
Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by SB in these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer. We identified point mutations in human pancreatic patient samples for another 11 CCGs, including Acvr2a and Map2k4. Importantly, 10% of the CCGs are involved in chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1, Fbxo11, and Vgll4, are also significantly associated with poor patient survival. SB mutagenesis provides a rich resource of mutations in potential cancer drivers for cross-comparative analyses with ongoing sequencing efforts in human pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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117. Integrating genomic binding site predictions using real-valued meta classifiers.
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Yi Sun, Robinson, Mark, Adams, Rod, Te Boekhorst, Rene, Rust, Alistair G., and Davey, Neil
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GENOMICS ,BINDING sites ,TRANSCRIPTION factors ,NUCLEOTIDE sequence ,ALGORITHMS - Abstract
Currently the best algorithms for predicting transcription factor binding sites in DNA sequences are severely limited in accuracy. There is good reason to believe that predictions from different classes of algorithms could be used in conjunction to improve the quality of predictions. In this paper, we apply single layer networks, rules sets, support vector machines and the Adaboost algorithm to predictions from 12 key real valued algorithms. Furthermore, we use a ‘window’ of consecutive results as the input vector in order to contextualise the neighbouring results. We improve the classification result with the aid of under- and over-sampling techniques. We find that support vector machines and the Adaboost algorithm outperform the original individual algorithms and the other classifiers employed in this work. In particular they give a better tradeoff between recall and precision. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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118. 19 - Evolving computational neural systems using synthetic developmental mechanisms
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Rust, Alistair G, Adams, Rod, Schilstra, Maria, and Bolouri, Hamid
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- 2003
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119. A data integration methodology for systems biology.
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Daehee Hwang, Rust, Alistair G., Ramsey, Stephen, Smith, Jennifer J., Leslie, Deena M., Weston, Andrea D., de Atauri, Pedro, Aitchison, John D., Hood, Leroy, Siegel, Andrew F., and Bolouri, Hamid
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TECHNOLOGY , *BIOTECHNOLOGY , *METHODOLOGY , *FIRE assay , *COMPUTER software , *OPEN source software - Abstract
Different experimental technologies measure different aspects of a system and to differing depth and breadth. High-throughput assays have inherently high false-positive and false-negative rates. Moreover, each technology includes systematic biases of a different nature. These differences make network reconstruction from multiple data sets difficult and error-prone. Additionally, because of the rapid rate of progress in biotechnology, there is usually no curated exemplar data set from which one might estimate data integration parameters. To address these concerns, we have developed data integration methods that can handle multiple data sets differing in statistical power, type, size, and network coverage without requiring a curated training data set. Our methodology is general in purpose and may be applied to integrate data from any existing and future technologies. Here we outline our methods and then demonstrate their performance by applying them to simulated data sets. The results show that these methods select true-positive data elements much more accurately than classical approaches. In an accompanying companion paper, we demonstrate the applicability of our approach to biological data. We have integrated our methodology into a free open source software package named POINTILLIST. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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120. Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia
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Van Der Weyden, Louise, Giotopoulos, George, Wong, Kim, Rust, Alistair G, Robles-Espinoza, Carla Daniela, Osaki, Hikari, Huntly, Brian J, and Adams, David J
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Repressor Proteins ,Disease Models, Animal ,Mice ,Oncogene Proteins, Fusion ,Proto-Oncogene Proteins c-ets ,Mutagenesis ,hemic and lymphatic diseases ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Core Binding Factor Alpha 2 Subunit ,PAX5 Transcription Factor ,Animals ,3. Good health ,Janus Kinases - Abstract
BACKGROUND: B-cell precursor acute lymphoblastic leukemia (B-ALL) is amongst the leading causes of childhood cancer-related mortality. Its most common chromosomal aberration is the ETV6-RUNX1 fusion gene, with ~25% of ETV6-RUNX1 patients also carrying PAX5 alterations. METHODS: We have recreated this mutation background by inter-crossing Etv6-RUNX1 (Etv6 (RUNX1-SB)) and Pax5(+/-) mice and performed an in vivo analysis to find driver genes using Sleeping Beauty transposon-mediated mutagenesis and also exome sequencing. RESULTS: Combination of Etv6-RUNX1 and Pax5(+/-) alleles generated a transplantable B220 + CD19+ B-ALL with a significant disease incidence. RNA-seq analysis showed a gene expression pattern consistent with arrest at the pre-B stage. Analysis of the transposon common insertion sites identified genes involved in B-cell development (Zfp423) and the JAK/STAT signaling pathway (Jak1, Stat5 and Il2rb), while exome sequencing revealed somatic hotspot mutations in Jak1 and Jak3 at residues analogous to those mutated in human leukemias, and also mutation of Trp53. CONCLUSIONS: Powerful synergies exists in our model suggesting STAT pathway activation and mutation of Trp53 are potent drivers of B-ALL in the context of Etv6-RUNX1;Pax5(+/-).
121. A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression
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Giotopoulos, George, Van Der Weyden, Louise, Osaki, Hikari, Rust, Alistair G., Gallipoli, Paolo, Meduri, Eshwar, Horton, Sarah J., Chan, Wai-In, Foster, Donna, Prinjha, Rab K., Pimanda, John E., Tenen, Daniel G., Vassiliou, George S., Koschmieder, Steffen, Adams, David J., and Huntly, Brian J. P.
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3. Good health - Abstract
Journal of experimental medicine : JEM 212(10), 1551-1569 (2015). doi:10.1084/jem.20141661, Published by Rockefeller Univ. Press, New York, NY
122. Acute sensitivity of the oral mucosa to oncogenic K-ras
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Van Der Weyden, Louise, Alcolea, Maria P, Jones, Philip H, Rust, Alistair G, Arends, Mark J, and Adams, David J
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Transcriptional Activation ,Hyperplasia ,Dose-Response Relationship, Drug ,Papilloma ,Reverse Transcriptase Polymerase Chain Reaction ,Mouth Mucosa ,Cell Differentiation ,3. Good health ,stomatognathic diseases ,Mice ,Sebaceous Glands ,Tamoxifen ,Cell Transformation, Neoplastic ,Genes, ras ,Animals ,Mouth Neoplasms ,Hair Follicle ,Proto-Oncogene Proteins c-akt ,Polymorphism, Restriction Fragment Length ,Cell Proliferation ,Signal Transduction - Abstract
Mouse models of cancer represent powerful tools for analysing the role of genetic alterations in carcinogenesis. Using a mouse model that allows tamoxifen-inducible somatic activation (by Cre-mediated recombination) of oncogenic K-ras(G12D) in a wide range of tissues, we observed hyperplasia of squamous epithelium located in moist or frequently abraded mucosa, with the most dramatic effects in the oral mucosa. This epithelium showed a sequence of squamous hyperplasia followed by squamous papilloma with dysplasia, in which some areas progressed to early invasive squamous cell carcinoma, within 14 days of widespread oncogenic K-ras activation. The marked proliferative response of the oral mucosa to K-ras(G12D) was most evident in the basal layers of the squamous epithelium of the outer lip with hair follicles and wet mucosal surface, with these cells staining positively for pAKT and cyclin D1, showing Ras/AKT pathway activation and increased proliferation with Ki-67 and EdU positivity. The stromal cells also showed gene activation by recombination and immunopositivity for pERK indicating K-Ras/ERK pathway activation, but without Ki-67 positivity or increase in stromal proliferation. The oral neoplasms showed changes in the expression pattern of cytokeratins (CK6 and CK13), similar to those observed in human oral tumours. Sporadic activation of the K-ras(G12D) allele (due to background spontaneous recombination in occasional cells) resulted in the development of benign oral squamous papillomas only showing a mild degree of dysplasia with no invasion. In summary, we show that oral mucosa is acutely sensitive to oncogenic K-ras, as widespread expression of activated K-ras in the murine oral mucosal squamous epithelium and underlying stroma can drive the oral squamous papilloma-carcinoma sequence.
123. Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015)
- Author
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Shay, Jerry W., Homma, Noriko, Zhou, Ruyun, Naseer, Muhammad Imran, Chaudhary, Adeel G., Al-Qahtani, Mohammed, Hirokawa, Nobutaka, Goudarzi, Maryam, Fornace, Albert J., Baeesa, Saleh, Hussain, Deema, Bangash, Mohammed, Alghamdi, Fahad, Schulten, Hans-Juergen, Carracedo, Angel, Khan, Ishaq, Qashqari, Hanadi, Madkhali, Nawal, Saka, Mohamad, Saini, Kulvinder S., Jamal, Awatif, Al-Maghrabi, Jaudah, Abuzenadah, Adel, Chaudhary, Adeel, Al Qahtani, Mohammed, Damanhouri, Ghazi, Alkhatabi, Heba, Goodeve, Anne, Crookes, Laura, Niksic, Nikolas, Beauchamp, Nicholas, Abuzenadah, Adel M., Vaught, Jim, Budowle, Bruce, Assidi, Mourad, Buhmeida, Abdelbaset, Merdad, Leena, Kumar, Sudhir, Miura, Sayaka, Gomez, Karen, Rasool, Mahmood, Rebai, Ahmed, Karim, Sajjad, Eldin, Hend F. Nour, Abusamra, Heba, Alhathli, Elham M., Salem, Nada, Al-Qahtani, Mohammed H., Faheem, Hossam, Agarwa, Ashok, Nieschlag, Eberhard, Wistuba, Joachim, Damm, Oliver S., Beg, Mohd A., Abdel-Meguid, Taha A., Mosli, Hisham A., Bajouh, Osama S., Coskun, Serdar, Abu-Elmagd, Muhammad, Dallol, Ashraf, Hakamy, Sahar, Al-Qahtani, Wejdan, Al-Harbi, Asia, Hussain, Shireen, Ozkosem, Burak, DuBois, Rick, Messaoudi, Safia S., Dandana, Maryam T., Mahjoub, Touhami, Almawi, Wassim Y., Abdalla, S., Al-Aama, M. Nabil, Elzawahry, Asmaa, Takahashi, Tsuyoshi, Mimaki, Sachiyo, Furukawa, Eisaku, Nakatsuka, Rie, Kurosaka, Isao, Nishigaki, Takahiko, Nakamura, Hiromi, Serada, Satoshi, Naka, Tetsuji, Hirota, Seiichi, Shibata, Tatsuhiro, Tsuchihara, Katsuya, Nishida, Toshirou, Kato, Mamoru, Mehmood, Sajid, Ashraf, Naeem Mahmood, Asif, Awais, Bilal, Muhammad, Mehmood, Malik Siddique, Hussain, Aadil, Jamal, Qazi Mohammad Sajid, Siddiqui, Mughees Uddin, Alzohairy, Mohammad A., Al Karaawi, Mohammad A., Nedjadi, Taoufik, Al-Khattabi, Heba, Al-Ammari, Adel, Al-Sayyad, Ahmed, Zitouni, Hédia, Raguema, Nozha, Ali, Marwa Ben, Malah, Wided, Lfalah, Raja, Almawi, Wassim, Elanbari, Mohammed, Ptitsyn, Andrey, Mahjoub, Sana, El Ghali, Rabeb, Achour, Bechir, Amor, Nidhal Ben, N’siri, Brahim, Morjani, Hamid, Azhar, Esam, Chayeb, Vera, Dendena, Maryam, Zitouni, Hedia, Zouari-Limayem, Khedija, Refaat, Bassem, Ashshi, Ahmed M., Batwa, Sarah A., Ramadan, Hazem, Awad, Amal, Ateya, Ahmed, El-Shemi, Adel Galal Ahmed, Ashshi, Ahmad, Basalamah, Mohammed, Na, Youjin, Yun, Chae-Ok, El-Shemi, Adel Galal, Kensara, Osama, Abdelfattah, Amr, Dheeb, Batol Imran, Al-Halbosiy, Mohammed M. F., Al lihabi, Rghad Kadhim, Khashman, Basim Mohammed, Laiche, Djouhri, Adeel, Chaudhary, Taoufik, Nedjadi, Al-Afghani, Hani, Łastowska, Maria, Al-Balool, Haya H., Sheth, Harsh, Mercer, Emma, Coxhead, Jonathan M., Redfern, Chris P. F., Peters, Heiko, Burt, Alastair D., Santibanez-Koref, Mauro, Bacon, Chris M., Chesler, Louis, Rust, Alistair G., Adams, David J., Williamson, Daniel, Clifford, Steven C., Jackson, Michael S., Singh, Mala, Mansuri, Mohmmad Shoab, Jadeja, Shahnawaz D., Patel, Hima, Marfatia, Yogesh S., Begum, Rasheedunnisa, Mohamed, Amal M., Kamel, Alaa K., Helmy, Nivin A., Hammad, Sayda A., Kayed, Hesham F., Shehab, Marwa I., El Gerzawy, Assad, Ead, Maha M., Ead, Ola M., Mekkawy, Mona, Mazen, Innas, El-Ruby, Mona, Shahid, S. M. A., Arif, J. M., Lohani, Mohtashim, Imen, Moumni, Leila, Chaouch, Houyem, Ouragini, Kais, Douzi, Fethi, Chaouachi Dorra Mellouli, Mohamed, Bejaoui, Salem, Abbes, Faggad, Areeg, Gebreslasie, Amanuel T., Zaki, Hani Y., Abdalla, Badreldin E., AlShammari, Maha S., Al-Ali, Rhaya, Al-Balawi, Nader, Al-Enazi, Mansour, Al-Muraikhi, Ali, Busaleh, Fadi, Al-Sahwan, Ali, Borgio, Francis, Sayyed, Abdulazeez, Al-Ali, Amein, Acharya, Sadananda, Zaki, Maha S., El-Bassyouni, Hala T., Elshal, Mohammed F., M., Kaleemuddin, Aldahlawi, Alia M., Saadah, Omar, McCoy, J. Philip, El-Tarras, Adel E., Awad, Nabil S., Alharthi, Abdulla A., Ibrahim, Mohamed M. M., Alsehli, Haneen S., Gari, Abdullah M., Abbas, Mohammed M., Kadam, Roaa A., Gari, Mazen M., Alkaff, Mohmmed H., Gari, Mamdooh A., eldin, Hend F. Nour, Moradi, Fatima A., Rashidi, Omran M., Awan, Zuhier A., Kaya, Ibrahim Hamza, Al-Harazi, Olfat, Colak, Dilek, Alkousi, Nabila A., Athanasopoulos, Takis, Bahmaid, Afnan O., Alhwait, Etimad A., Alkaf, Mohammed H., Kadam, Roaa, Kalamegam, Gauthaman, Alhathli, Elham, Alsayed, Salma N., Aljohani, Fawziah H., Habeeb, Samaher M., Almashali, Rawan A., Basit, Sulman, Ahmed, Samia M., Sharma, Rakesh, Agarwal, Ashok, Durairajanayagam, Damayanthi, Samanta, Luna, Sabanegh, Edmund S., Cui, Zhihong, Alboogmi, Alaa A., Alansari, Nuha A., Al-Quaiti, Maha M., Ashgan, Fai T., Bandah, Afnan, Jamal, Hasan S., Rozi, Abdullraheem, Mirza, Zeenat, Al Sayyad, Ahmad J., Farsi, Hasan M. A., Al-Maghrabi, Jaudah A., Alotibi, Reem, Al-Ahmadi, Alaa, Albogmi, Alaa A., Ebiya, Rasha A., Darwish, Samia M., Montaser, Metwally M., Bajic, Vladimir B., Gomaa, Wafaey, Hanbazazh, Mehenaz, Al-Ahwal, Mahmoud, Hakamy, Saher, Baba, Ghali, Al-Harbi, Abdullah, Baba, Ghalia, Eldin, Hend Nour, Alyamani, Aisha A., Gadi, Rawan, Alfakeeh, Saadiah M., Ghazala, Rubi, Mathew, Shilu, Hamed, M. Haroon, Qadri, Ishtiaq, Mira, Lobna, Shaabad, Manal, Almutairi, Mikhlid H., Ambers, Angie, Churchill, Jennifer, King, Jonathan, Stoljarova, Monika, Gill-King, Harrell, Al-Qatani, Muhammad, Ahmed, Farid, Almagd, Taha Abo, Al-Qahtani, Muhammad, Buhmaida, Abdelbaset, Satar, Rukhsana, Ahmad, Waseem, Nazam, Nazia, Lone, Mohamad I., Naseer, Muhammad I., Jamal, Mohammad S., Zaidi, Syed K., Pushparaj, Peter N., Jafri, Mohammad A., Ansari, Shakeel A., Alqahtani, Mohammed H., Bashier, Hanan, Al Qahtani, Abrar, Nour, Amal M., Zenadah, Adel M. Abu, Al Qahtani, Muhammed, Faheem, Muhammad, Mathew, Shiny, Pushparaj, Peter Natesan, Al-Qahtani, Mohammad H., Alhadrami, Hani A., Hussein, Ibtessam R., Bader, Rima S., Bassiouni, Randa, Alquaiti, Maha, Ashgan, Fai, Schulten, Hans, Alama, Mohamed Nabil, Al Qahtani, Mohammad H., Lone, Mohammad I., Nizam, Nazia, Al-Qahtani, Muhammed H., Alshihri, Eradah, Alharbi, Lina, Natesan, Peter Pushparaj, Khan, Fazal, Sait, Khalid Hussain Wali, Anfinan, Nisreen, Mira, Lobna S., AlQahtani, Mohammed H., Sogaty, Sameera, Bassiouni, Randa I., Sibiani, Abdulrahman M. S., Warsi, Mohiuddin K., Rubi, Kumar, Kundan, Naqvi, Ahmad A. T., Ahmad, Faizan, Hassan, Md I., Ali, Ashraf, Jarullah, Jummanah, Buhmeida, Abdelbasit, Khan, Shahida, Abdussami, Ghufrana, Mahfooz, Maryam, Kamal, Mohammad A., Damanhouri, Ghazi A., Jarullah, Bushra, Jarullah, Mohammad S. S., Bajouh, Osama, Mathkoor, Abdulah E. A., Alsalmi, Hashim M. A., Oun, Anas M. M., Damanhauri, Ghazi A., Chudhary, Adeel G., Abutalib, Yousif A., Merico, Daniele, Walker, Susan, Marshall, Christian R., Zarrei, Mehdi, Scherer, Stephen W., Ashgan, Fai Talal, Zaidi, Syed Kashif, Jan, Mohammed M., Al-Zahrani, Maryam, Lary, Sahira, Dermitzakis, Emmanuel, Al-refai, Abeer A., Saleh, Mona, Yassien, Rehab I., Kamel, Mahmmoud, Habeb, Rabab M., Filimban, Najlaa, Ghannam, Nadia, Abuzenadah, Adel Mohammed, Bibi, Fehmida, Akhtar, Sana, Azhar, Esam I., Yasir, Muhammad, Nasser, Muhammad I., Jiman-Fatani, Asif A., Sawan, Ali, Lahzah, Ruaa A., Ali, Asho, Hassan, Syed A., Hasnain, Seyed E., Tayubi, Iftikhar A., Abujabal, Hamza A., Magrabi, Alaa O., Abuzenada, Adel, Kumosani, Taha Abduallah, Barbour, Elie, Shabaad, Manal, Merdad, Adnan, Gauthaman, Kalamegam, Gari, Mamdooh, Aljahdali, Hani M. A., Al Nono, Reham, Alsehli, Haneen, Abbas, Mohammed, Jamal, Mohammed Sarwar, Ansari, Shakeel, Alghamdi, Mansour A., Shamy, Magdy, Costa, Max, Khoder, Mamdouh I., Kharrat, Najla, Belmabrouk, Sabrine, Abdelhedi, Rania, Benmarzoug, Riadh, Al Qahtani, Mohammed H., Dhamanhouri, Ghazi, Noorwali, Abdelwahab, Alwasiyah, Mohammad Khalid, Bahamaid, Afnan, Alfakeeh, Saadiah, Alyamani, Aisha, Mobasheri, Ali, Jamal, Mohammad Sarwar, Khan, Raziuddin, Bhatia, Kanchan, Ahmad, Saif, AslamTayubi, Iftikhar, Tripathi, Manish, Hassan, Syed Asif, Shrivastava, Rahul, Hassan, Syed, Abujabal, Hamza A. S., Shah, Ishani, Sheikh, Ishfaq A., Ahmad, Ejaz, Rehan, Mohd, AlBasri, Samera F., Turki, Rola F., Hammoudah, Sahar A. F., AlHarbi, Khalid M., El-Attar, Lama M., Darwish, Ahmed M. Z., Ibrahim, Sara M., Choudhry, Hani, Awlia, Jalaludden, khan, Imran, Al-basri, Sameera, Kumosani, Taha, EL Sayed, Heba M., Hafez, Eman A., Elaimi, Aisha Hassan, Bassiouni, Randa Ibrahim, Wintle, Richard F., Pillai, Vikram Gopalakrishna, Sharma, Sujata, Kaur, Punit, Srinivasan, Alagiri, Singh, Tej P., Al-Adwani, Fatima, Hussein, Deema, Al-Sharif, Mona, Al-Ghamdi, Fahad, Baeesa, Saleh S., Kumosani, Taha Abdullah, Al-Allaf, Faisal A., Abduljaleel, Zainularifeen, Alashwal, Abdullah, Taher, Mohiuddin M., Bouazzaoui, Abdellatif, Abalkhail, Halah, Ba-Hammam, Faisal A., Athar, Mohammad, Sait, Khalid HussainWali, Mami, Naira Ben, Haffani, Yosr Z., Medhioub, Mouna, Hamzaoui, Lamine, Cherif, Ameur, Azouz, Msadok, Nasser, Mohammed Imran, Turkistany, Shereen A., Al-harbi, Lina M., Sabir, Jamal, Al-Madoudi, Basmah, Al-Aslani, Bayan, Al-Harbi, Khulud, Al-Jahdali, Rwan, Qudaih, Hanadi, Al Hamzy, Emad, Ilyas, Asad M., Ahmed, Youssri, Alqahtani, Mohammed, Alamandi, Alaa, Subhi, Ohoud, Bagatian, Nadia, Al-Johari, Adel, Al-Hamour, Osman Abdel, Al-Aradati, Hosam, Al-Mutawa, Abdulmonem, Al-Mashat, Faisal, Al-Qahtani, Mohammad, shah, Muhammad W., Azhar, Esam I, Al-Masoodi, Saad, Khamla, Emna, Jlassi, Chaima, Masmoudi, Ahmed S., Belbahri, Lassaad, Al-Khayyat, Shadi, Attas, Roba, Abu-Sanad, Atlal, Abuzinadah, Mohammed, Bouazzi, Habib, Trujillo, Carlos, Alotaibi, Maha, Nassir, Rami, Jiffri, Essam H., Ashraf, Ghulam M., Aziz, Mohammad A., Ali, Rizwan, Samman, Nusaibah, Periyasamy, Sathish, Aldress, Mohammed, Al Otaibi, Majed, Al Yousef, Zeyad, Boudjelal, Mohamed, AlAbdulkarim, Ibrahim, Suhail, Mohd, Qureshi, Abid, Jamal, Adil, El-Readi, Mahmoud Z., Eid, Safaa Y., Wink, Michael, Isa, Ahmed M., Alnuaim, Lulu, Almutawa, Johara, Abu-Rafae, Basim, Alasiri, Saleh, Binsaleh, Saleh, and Alqahtani, Mohamed H.
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Genetics ,Meeting Abstracts ,Biotechnology - Abstract
Table of contents O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa O3 Integration of metagenomics and metabolomics in gut microbiome research Maryam Goudarzi, Albert J. Fornace Jr. O4 A unique integrated system to discern pathogenesis of central nervous system tumors Saleh Baeesa, Deema Hussain, Mohammed Bangash, Fahad Alghamdi, Hans-Juergen Schulten, Angel Carracedo, Ishaq Khan, Hanadi Qashqari, Nawal Madkhali, Mohamad Saka, Kulvinder S. Saini, Awatif Jamal, Jaudah Al-Maghrabi, Adel Abuzenadah, Adeel Chaudhary, Mohammed Al Qahtani, Ghazi Damanhouri O5 RPL27A is a target of miR-595 and deficiency contributes to ribosomal dysgenesis Heba Alkhatabi O6 Next generation DNA sequencing panels for haemostatic and platelet disorders and for Fanconi anaemia in routine diagnostic service Anne Goodeve, Laura Crookes, Nikolas Niksic, Nicholas Beauchamp O7 Targeted sequencing panels and their utilization in personalized medicine Adel M. Abuzenadah O8 International biobanking in the era of precision medicine Jim Vaught O9 Biobank and biodata for clinical and forensic applications Bruce Budowle, Mourad Assidi, Abdelbaset Buhmeida O10 Tissue microarray technique: a powerful adjunct tool for molecular profiling of solid tumors Jaudah Al-Maghrabi O11 The CEGMR biobanking unit: achievements, challenges and future plans Abdelbaset Buhmeida, Mourad Assidi, Leena Merdad O12 Phylomedicine of tumors Sudhir Kumar, Sayaka Miura, Karen Gomez O13 Clinical implementation of pharmacogenomics for colorectal cancer treatment Angel Carracedo, Mahmood Rasool O14 From association to causality: translation of GWAS findings for genomic medicine Ahmed Rebai O15 E-GRASP: an interactive database and web application for efficient analysis of disease-associated genetic information Sajjad Karim, Hend F Nour Eldin, Heba Abusamra, Elham M Alhathli, Nada Salem, Mohammed H Al-Qahtani, Sudhir Kumar O16 The supercomputer facility “AZIZ” at KAU: utility and future prospects Hossam Faheem O17 New research into the causes of male infertility Ashok Agarwa O18 The Klinefelter syndrome: recent progress in pathophysiology and management Eberhard Nieschlag, Joachim Wistuba, Oliver S. Damm, Mohd A. Beg, Taha A. Abdel-Meguid, Hisham A. Mosli, Osama S. Bajouh, Adel M. Abuzenadah, Mohammed H. Al-Qahtani O19 A new look to reproductive medicine in the era of genomics Serdar Coskun P1 Wnt signalling receptors expression in Saudi breast cancer patients Muhammad Abu-Elmagd, Abdelbaset Buhmeida, Ashraf Dallol, Jaudah Al-Maghrabi, Sahar Hakamy, Wejdan Al-Qahtani, Asia Al-Harbi, Shireen Hussain, Mourad Assidi, Mohammed Al-Qahtani, Adel Abuzenadah P2 Analysis of oxidative stress interactome during spermatogenesis: a systems biology approach to reproduction Burak Ozkosem, Rick DuBois P3 Interleukin-18 gene variants are strongly associated with idiopathic recurrent pregnancy loss. Safia S Messaoudi, Maryam T Dandana, Touhami Mahjoub, Wassim Y Almawi P4 Effect of environmental factors on gene-gene and gene-environment reactions: model and theoretical study applied to environmental interventions using genotype S. Abdalla, M. Nabil Al-Aama P5 Genomics and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumor Asmaa Elzawahry, Tsuyoshi Takahashi, Sachiyo Mimaki, Eisaku Furukawa, Rie Nakatsuka, Isao Kurosaka, Takahiko Nishigaki, Hiromi Nakamura, Satoshi Serada, Tetsuji Naka, Seiichi Hirota, Tatsuhiro Shibata, Katsuya Tsuchihara, Toshirou Nishida, Mamoru Kato P6 In-Silico analysis of putative HCV epitopes against Pakistani human leukocyte antigen background: an approach towards development of future vaccines for Pakistani population Sajid Mehmood, Naeem Mahmood Ashraf, Awais Asif, Muhammad Bilal, Malik Siddique Mehmood, Aadil Hussain P7 Inhibition of AChE and BuChE with the natural compounds of Bacopa monerri for the treatment of Alzheimer’s disease: a bioinformatics approach Qazi Mohammad Sajid Jamal, Mughees Uddin Siddiqui, Mohammad A. Alzohairy, Mohammad A. Al Karaawi P8 Her2 expression in urothelial cell carcinoma of the bladder in Saudi Arabia Taoufik Nedjadi, Jaudah Al-Maghrabi, Mourad Assidi, Heba Al-Khattabi, Adel Al-Ammari, Ahmed Al-Sayyad, Abdelbaset Buhmeida, Mohammed Al-Qahtani P9 Association of angiotensinogen single nucleotide polymorphisms with Preeclampsia in patients from North Africa Hédia Zitouni, Nozha Raguema, Marwa Ben Ali, Wided Malah, Raja Lfalah, Wassim Almawi, Touhami Mahjoub P10 Systems biology analysis reveals relations between normal skin, benign nevi and malignant melanoma Mohammed Elanbari, Andrey Ptitsyn P11 The apoptotic effect of thymoquinone in Jurkat cells Sana Mahjoub, Rabeb El Ghali, Bechir Achour, Nidhal Ben Amor, Mourad Assidi, Brahim N'siri, Hamid Morjani P12 Sonic hedgehog contributes in bladder cancer invasion in Saudi Arabia Taoufik Nedjadi, Adel Al-Ammari, Ahmed Al-Sayyad, Nada Salem, Esam Azhar, Jaudah Al-Maghrabi P13 Association of Interleukin 18 gene promoter polymorphisms - 607A/C and -137 G/C with colorectal cancer onset in a sample of Tunisian population Vera Chayeb, Maryam Dendena, Hedia Zitouni, Khedija Zouari-Limayem, Touhami Mahjoub P14 Pathological expression of interleukin-6, -11, leukemia inhibitory factor and their receptors in tubal gestation with and without tubal cytomegalovirus infection Bassem Refaat, Ahmed M Ashshi, Sarah A Batwa P15 Phenotypic and genetic profiling of avian pathogenic and human diarrhegenic Escherichia coli in Egypt Hazem Ramadan, Amal Awad, Ahmed Ateya P16 Cancer-targeting dual gene virotherapy as a promising therapeutic strategy for treatment of hepatocellular carcinoma Adel Galal Ahmed El-Shemi, Ahmad Ashshi, Mohammed Basalamah, Youjin Na, Chae-Ok YUN P17 Cancer dual gene therapy with oncolytic adenoviruses expressing TRAIL and IL-12 transgenes markedly eradicated human hepatocellular carcinoma both in vitro and in vivo Adel Galal Ahmed El-Shemi, Ahmad Ashshi, Mohammed Basalamah, Youjin Na, Chae-Ok Yun P18 Therapy with paricalcitol attenuates tumor growth and augments tumoricidal and anti-oncogenic effects of 5-fluorouracil on animal model of colon cancer Adel Galal El-Shemi, Bassem Refaat, Osama Kensara, Amr Abdelfattah P19 The effects of Rubus idaeus extract on normal human lymphocytes and cancer cell line Batol Imran Dheeb, Mohammed M. F. Al-Halbosiy, Rghad Kadhim Al lihabi, Basim Mohammed Khashman P20 Etanercept, a TNF-alpha inhibitor, alleviates mechanical hypersensitivity and spontaneous pain in a rat model of chemotherapy-induced neuropathic pain Djouhri, Laiche, Chaudhary Adeel, Nedjadi, Taoufik P21 Sleeping beauty mutagenesis system identified genes and neuronal transcription factor network involved in pediatric solid tumour (medulloblastoma) Hani Al-Afghani, Maria Łastowska, Haya H Al-Balool, Harsh Sheth, Emma Mercer, Jonathan M Coxhead, Chris PF Redfern, Heiko Peters, Alastair D Burt, Mauro Santibanez-Koref, Chris M Bacon, Louis Chesler, Alistair G Rust, David J Adams, Daniel Williamson, Steven C Clifford, Michael S Jackson P22 Involvement of interleukin-1 in vitiligo pathogenesis Mala Singh, Mohmmad Shoab Mansuri, Shahnawaz D. Jadeja, Hima Patel, Yogesh S. Marfatia, Rasheedunnisa Begum P23 Cytogenetics abnormalities in 12,884 referred population for chromosomal analysis and the role of FISH in refining the diagnosis (cytogenetic experience 2004-2013) Amal M Mohamed, Alaa K Kamel, Nivin A Helmy, Sayda A Hammad, Hesham F Kayed, Marwa I Shehab, Assad El Gerzawy, Maha M. Ead, Ola M Ead, Mona Mekkawy, Innas Mazen, Mona El-Ruby P24 Analysis of binding properties of angiotensin-converting enzyme 2 through in silico method S. M. A. Shahid, Qazi Mohammad Sajid Jamal, J. M. Arif, Mohtashim Lohani P25 Relationship of genetics markers cis and trans to the β-S globin gene with fetal hemoglobin expression in Tunisian sickle cell patients Moumni Imen, Chaouch Leila, Ouragini Houyem, Douzi Kais, Chaouachi Dorra Mellouli Fethi, Bejaoui Mohamed, Abbes Salem P26 Analysis of estrogen receptor alpha gene polymorphisms in breast cancer: link to genetic predisposition in Sudanese women Areeg Faggad, Amanuel T Gebreslasie, Hani Y Zaki, Badreldin E Abdalla P27 KCNQI gene polymorphism and its association with CVD and T2DM in the Saudi population Maha S AlShammari, Rhaya Al-Ali, Nader Al-Balawi , Mansour Al-Enazi, Ali Al-Muraikhi, Fadi Busaleh, Ali Al-Sahwan, Francis Borgio, Abdulazeez Sayyed, Amein Al-Ali, Sadananda Acharya P28 Clinical, neuroimaging and cytogenetic study of a patient with microcephaly capillary malformation syndrome Maha S. Zaki, Hala T. El-Bassyouni, Marwa I. Shehab P29 Altered expression of CD200R1 on dendritic cells of patients with inflammatory bowel diseases: in silico investigations and clinical evaluations Mohammed F. Elshal, Kaleemuddin M., Alia M. Aldahlawi, Omar Saadah, J. Philip McCoy P30 Development of real time PCR diagnostic protocol specific for the Saudi Arabian H1N1 viral strains Adel E El-Tarras, Nabil S Awad, Abdulla A Alharthi, Mohamed M M Ibrahim P31 Identification of novel genetic variations affecting Osteoarthritis patients Haneen S Alsehli, Ashraf Dallol, Abdullah M Gari, Mohammed M Abbas, Roaa A Kadam, Mazen M. Gari, Mohmmed H Alkaff, Adel M Abuzenadah, Mamdooh A Gari P32 An integrated database of GWAS SNVs and their evolutionary properties Heba Abusamra, Sajjad Karim, Hend F Nour eldin, Elham M Alhathli, Nada Salem, Sudhir Kumar, Mohammed H Al-Qahtani P33 Familial hypercholesterolemia in Saudi Arabia: prime time for a national registry and genetic analysis Fatima A. Moradi, Omran M. Rashidi, Zuhier A. Awan P34 Comparative genomics and network-based analyses of early hepatocellular carcinoma Ibrahim Hamza Kaya, Olfat Al-Harazi, Dilek Colak P35 A TALEN-based oncolytic viral vector approach to knock out ABCB1 gene mediated chemoresistance in cancer stem cells Nabila A Alkousi, Takis Athanasopoulos P36 Cartilage differentiation and gene expression of synovial fluid mesenchymal stem cells derived from osteoarthritis patients Afnan O Bahmaid, Etimad A Alhwait, Mamdooh A Gari, Haneen S Alsehli, Mohammed M Abbas, Mohammed H Alkaf, Roaa Kadam, Ashraf Dallol, Gauthaman Kalamegam P37 E-GRASP: Adding an evolutionary component to the genome-wide repository of associations (GRASP) resource Hend F Nour Eldin, Sajjad Karim, Heba Abusamra, Elham Alhathli, Nada Salem, Mohammed H Al-Qahtani, Sudhir Kumar P38 Screening of AGL gene mutation in Saudi family with glycogen storage disease Type III Salma N Alsayed, Fawziah H Aljohani, Samaher M Habeeb, Rawan A Almashali, Sulman Basit, Samia M Ahmed P39 High throughput proteomic data suggest modulation of cAMP dependent protein kinase A and mitochondrial function in infertile patients with varicocele Rakesh Sharma, Ashok Agarwal, Damayanthi Durairajanayagam, Luna Samanta, Muhammad Abu-Elmagd, Adel M. Abuzenadah, Edmund S. Sabanegh, Mourad Assidi, Mohammed Al-Qahtani P40 Significant protein profile alterations in men with primary and secondary infertility Ashok Agarwal, Rakesh Sharma, Luna Samanta, Damayanthi Durairajanayagam, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani, Adel M. Abuzenadah, Edmund S. Sabanegh P41 Spermatozoa maturation in infertile patients involves compromised expression of heat shock proteins Luna Samanta, Ashok Agarwal, Rakesh Sharma, Zhihong Cui, Mourad Assidi, Adel M. Abuzenadah, Muhammad Abu-Elmagd, Mohammed Al-Qahtani P42 Array comparative genomic hybridization approach to search genomic answers for spontaneous recurrent abortion in Saudi Arabia Alaa A Alboogmi, Nuha A Alansari, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Hasan S Jamal, Abdullraheem Rozi, Zeenat Mirza, Adel M Abuzenadah, Sajjad Karim, Mohammed H Al-Qahtani P43 Global gene expression profiling of Saudi kidney cancer patients Sajjad Karim, Hans-Juergen Schulten, Ahmad J Al Sayyad, Hasan MA Farsi, Jaudah A Al-Maghrabi, Zeenat Mirza, Reem Alotibi, Alaa Al-Ahmadi, Nuha A Alansari, Alaa A Albogmi, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Mohammed H Al-Qahtani P44 Downregulated StAR gene and male reproductive dysfunction caused by nifedipine and ethosuximide Rasha A Ebiya, Samia M Darwish, Metwally M. Montaser P45 Clustering based gene expression feature selection method: A computational approach to enrich the classifier efficiency of differentially expressed genes Heba Abusamra, Vladimir B. Bajic P46 Prognostic significance of Osteopontin expression profile in colorectal carcinoma Jaudah Al-Maghrabi, Wafaey Gomaa, Mehenaz Hanbazazh, Mahmoud Al-Ahwal, Asia Al-Harbi, Wejdan Al-Qahtani, Saher Hakamy, Ghali Baba, Abdelbaset Buhmeida, Mohammed Al-Qahtani P47 High Glypican-3 expression pattern predicts longer disease-specific survival in colorectal carcinoma Jaudah Al-Maghrabi, Abdullah Al-Harbi, Mahmoud Al-Ahwal, Asia Al-Harbi, Wejdan Al-Qahtani, Sahar Hakamy, Ghalia Baba, Abdelbaset Buhmeida, Mohammed Al-Qahtani P48 An evolutionary re-assessment of GWAS single nucleotide variants implicated in the Cholesterol traits Elham M Alhathli, Sajjad Karim, Nada Salem, Hend Nour Eldin, Heba Abusamra, Sudhir Kumar, Mohammed H Al-Qahtani P49 Derivation and characterization of human Wharton’s jelly stem cells (hWJSCs) in vitro for future therapeutic applications Aisha A Alyamani, Gauthaman Kalamegam, Etimad A Alhwait, Mamdooh A Gari, Mohammed M Abbas, Mohammed H Alkaf, Haneen S Alsehli, Roaa A Kadam, Mohammed Al-Qahtani P50 Attitudes of healthcare students toward biomedical research in the post-genomic era Rawan Gadi, Abdelbaset Buhmeida, Mourad Assidi , Adeel Chaudhary, Leena Merdad P51 Evaluation of the immunomodulatory effects of thymoquinone on human bone marrow mesenchymal stem cells (BM-MSCs) from osteoarthritic patients Saadiah M Alfakeeh, Etimad A Alhwait, Mamdooh A Gari, Mohammed M Abbas, Mohammed H Alkaf, Haneen S Alsehli, Roaa Kadam, Gauthaman Kalamegam P52 Implication of IL-10 and IL-28 polymorphism with successful anti-HCV therapy and viral clearance Rubi Ghazala, Shilu Mathew, M.Haroon Hamed, Mourad Assidi, Mohammed Al-Qahtani, Ishtiaq Qadri P53 Selection of flavonoids against obesity protein (FTO) using in silico and in vitro approaches Shilu Mathew, Lobna Mira, Manal Shaabad, Shireen Hussain, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani P54 Computational selection and in vitro validation of flavonoids as new antidepressant agents Shilu Mathew, Manal Shaabad, Lobna Mira, Shireen Hussain, Mourad Assidi, Muhammad Abu-Elmagd, Mohammed Al-Qahtani P55 In Silico prediction and prioritization of aging candidate genes associated with progressive telomere shortening Ahmed Rebai, Mourad Assidi, Abdelbaset Buhmeida, Muhammad Abu-Elmagd, Ashraf Dallol, Jerry W Shay P56 Identification of new cancer testis antigen genes in diverse types of malignant human tumour cells Mikhlid H Almutairi P57 More comprehensive forensic genetic marker analyses for accurate human remains identification using massively parallel sequencing (MPS) Angie Ambers, Jennifer Churchill, Jonathan King, Monika Stoljarova, Harrell Gill-King, Mourad Assidi, Muhammad Abu-Elmagd, Abdelbaset Buhmeida, Muhammad Al-Qatani, Bruce Budowle P58 Flow cytometry approach towards treatment men infertility in Saudi Arabia Muhammad Abu-Elmagd, Farid Ahmed, Ashraf Dallol, Mourad Assidi, Taha Abo Almagd, Sahar Hakamy, Ashok Agarwal, Muhammad Al-Qahtani, Adel Abuzenadah P59 Tissue microarray based validation of CyclinD1 expression in renal cell carcinoma of Saudi kidney patients Sajjad Karim, Hans-Juergen Schulten, Ahmad J Al Sayyad, Hasan MA Farsi, Jaudah A Al-Maghrabi, Abdelbaset Buhmaida, Zeenat Mirza, Reem Alotibi, Alaa Al-Ahmadi, Nuha A Alansari, Alaa A Albogmi, Maha M Al-Quaiti, Fai T Ashgan, Afnan Bandah, Mohammed H Al-Qahtani P60 Assessment of gold nanoparticles in molecular diagnostics and DNA damage studies Rukhsana Satar, Mahmood Rasool, Waseem Ahmad, Nazia Nazam, Mohamad I Lone, Muhammad I Naseer, Mohammad S Jamal, Syed K Zaidi, Peter N Pushparaj, Mohammad A Jafri, Shakeel A Ansari, Mohammed H Alqahtani P61 Surfing the biospecimen management and processing workflow at CEGMR Biobank Hanan Bashier, Abrar Al Qahtani, Shilu Mathew, Amal M. Nour, Heba Alkhatabi, Adel M. Abu Zenadah, Abdelbaset Buhmeida, Mourad Assidi, Muhammed Al Qahtani P62 Autism Spectrum Disorder: knowledge, attitude and awareness in Jeddah, Kingdom of Saudi Arabia Muhammad Faheem, Shilu Mathew, Shiny Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani P63 Simultaneous genetic screening of the coagulation pathway genes using the Thromboscan targeted sequencing panel Hani A. Alhadrami, Ashraf Dallol, Adel Abuzenadah P64 Genome wide array comparative genomic hybridization analysis in patients with syndromic congenital heart defects Ibtessam R. Hussein, Adeel G. Chaudhary, Rima S Bader, Randa Bassiouni, Maha Alquaiti, Fai Ashgan, Hans Schulten, Mohamed Nabil Alama, Mohammad H. Al Qahtani P65 Toxocogenetic evaluation of 1, 2-Dichloroethane in bone marrow, blood and cells of immune system using conventional, molecular and flowcytometric approaches Mohammad I Lone, Nazia Nizam, Waseem Ahmad, Mohammad A Jafri, Mahmood Rasool, Shakeel A Ansari, Muhammed H Al-Qahtani P66 Molecular cytogenetic diagnosis of sexual development disorders in newborn: A case of ambiguous genitalia Eradah Alshihri, Muhammad Abu-Elmagd, Lina Alharbi, Mourad Assidi, Mohammed Al-Qahtani P67 Identification of disease specific gene expression clusters and pathways in hepatocellular carcinoma using In Silico methodologies Shilu Mathew, Peter Pushparaj Natesan, Muhammed Al Qahtani P68 Human Wharton’s Jelly stem cell conditioned medium inhibits primary ovarian cancer cells in vitro: Identification of probable targets and mechanisms using systems biology Gauthaman Kalamegam, Peter Natesan Pushparaj, Fazal Khan, Roaa Kadam, Farid Ahmed, Mourad Assidi, Khalid Hussain Wali Sait, Nisreen Anfinan, Mohammed Al Qahtani P69 Mutation spectrum of ASPM (Abnormal Spindle-like, Microcephaly-associated) gene in Saudi Arabian population Muhammad I Naseer, Adeel G Chaudhary, Mohammad S Jamal, Shilu Mathew, Lobna S Mira, Peter N Pushparaj, Shakeel A Ansari, Mahmood Rasool, Mohammed H AlQahtani P70 Identification and characterization of novel genes and mutations of primary microcephaly in Saudi Arabian population Muhammad I Naseer, Adeel G Chaudhary, Shilu Mathew, Lobna S Mira, Mohammad S Jamal, Sameera Sogaty, Randa I Bassiouni, Mahmood Rasool, Mohammed H AlQahtani P71 Molecular genetic analysis of hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in Saudi Arabian population Mahmood Rasool, Shakeel A Ansari, Mohammad S Jamal, Peter N Pushparaj, Abdulrahman MS Sibiani, Waseem Ahmad, Abdelbaset Buhmeida, Mohammad A Jafri, Mohiuddin K Warsi, Muhammad I Naseer, Mohammed H Al-Qahtani P72 Function predication of hypothetical proteins from genome database of chlamydia trachomatis Rubi, Kundan Kumar, Ahmad AT Naqvi, Faizan Ahmad, Md I Hassan, Mohammad S Jamal, Mahmood Rasool, Mohammed H AlQahtani P73 Transcription factors as novel molecular targets for skin cancer Ashraf Ali, Jummanah Jarullah, Mahmood Rasool, Abdelbasit Buhmeida, Shahida Khan, Ghufrana Abdussami, Maryam Mahfooz, Mohammad A Kamal, Ghazi A Damanhouri, Mohammad S Jamal P74 An In Silico analysis of Plumbagin binding to apoptosis executioner: Caspase-3 and Caspase-7 Bushra Jarullah, Jummanah Jarullah, Mohammad SS Jarullah, Ashraf Ali, Mahmood Rasool, Mohammad S Jamal P75 Single cell genomics applications for preimplantation genetic screening optimization: Comparative analysis of whole genome amplification technologies Mourad Assidi, Muhammad Abu-Elmagd, Osama Bajouh, Peter Natesan Pushparaj, Mohammed Al-Qahtani, Adel Abuzenadah P76 ZFP36 regulates miRs-34a in anti-IgM triggered immature B cells Mohammad S Jamal, Jummanah Jarullah, Abdulah EA Mathkoor, Hashim MA Alsalmi, Anas MM Oun, Ghazi A Damanhauri, Mahmood Rasool, Mohammed H AlQahtani P77 Identification of a novel mutation in the STAMBP gene in a family with microcephaly-capillary malformation syndrome Muhammad I. Naseer, Mahmood Rasool, Sameera Sogaty, Adeel G. Chudhary, Yousif A. Abutalib, Daniele Merico, Susan Walker, Christian R. Marshall, Mehdi Zarrei, Stephen W. Scherer, Mohammad H. Al-Qahtani P78 Copy number variations in Saudi patients with intellectual disability and epilepsy Muhammad I. Naseer, Muhammad Faheem, Adeel G. Chaudhary, Mahmood Rasool, Gauthaman Kalamegam, Fai Talal Ashgan, Mourad Assidi, Farid Ahmed, Syed Kashif Zaidi, Mohammed M. Jan, Mohammad H. Al-Qahtani P79 Prognostic significance of CD44 expression profile in colorectal carcinoma Maryam Al-Zahrani, Sahira Lary, Sahar Hakamy, Ashraf Dallol, Mahmoud Al-Ahwal, Jaudah Al-Maghrabi, Emmanuel Dermitzakis, Adel Abuzenadah, Abdelbaset Buhmeida, Mohammed Al-Qahtani P80 Association of the endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications Abeer A Al-refai, Mona Saleh, Rehab I Yassien, Mahmmoud Kamel, Rabab M Habeb P81 SNPs array to screen genetic variation among diabetic patients Najlaa Filimban, Ashraf Dallol, Nadia Ghannam, Mohammed Al-Qahtani, Adel Mohammed Abuzenadah P82 Detection and genotyping of Helicobacter pylori among gastric cancer patients from Saudi Arabian population Fehmida Bibi, Sana Akhtar, Esam I. Azhar, Muhammad Yasir, Muhammad I. Nasser, Asif A. Jiman-Fatani, Ali Sawan P83 Antimicrobial drug resistance and molecular detection of susceptibility to Fluoroquinolones among clinical isolates of Salmonella species from Jeddah-Saudi Arabia Ruaa A Lahzah, Asho Ali P84 Identification of the toxic and virulence nature of MAP1138c protein of Mycobacterium avium subsp. paratuberculosis Syed A Hassan, Seyed E Hasnain, Iftikhar A Tayubi, Hamza A Abujabal, Alaa O Magrabi P85 In vitro and in silico evaluation of miR137 in human breast cancer Fazal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adel Abuzenada, Taha Abduallah Kumosani, Elie Barbour, Mohammed Al-Qahtani P86 Auruka gene is over-expressed in Saudi breast cancer Manal Shabaad, Shilu Mathew, Ashraf Dallol, Adnan Merdad, Abdelbaset Buhmeida, Mohammed Al-Qahtani P87 The potential of immunogenomics in personalized healthcare Mourad Assidi, Muhammad Abu-Elmagd, Kalamegam Gauthaman, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Peter Natesan Pushparaj, Mohammed Al-Qahtani P88 In Silico physiochemical and structural characterization of a putative ORF MAP0591 and its implication in the pathogenesis of Mycobacterium paratuberculosis in ruminants and humans Syed A Hassan, Iftikhar A Tayubi, Hani MA Aljahdali P89 Effects of heat shock on human bone marrow mesenchymal stem cells (BM-MSCs): Implications in regenerative medicine Reham Al Nono, Mamdooh Gari, Haneen Alsehli, Farid Ahmed, Mohammed Abbas, Gauthaman Kalamegam, Mohammed Al-Qahtani P90 In Silico analyses of the molecular targets of Resveratrol unravels its importance in mast cell mediated allergic responses Shilu Mathew, Fazal Khan, Mahmood Rasool, Mohammed Sarwar Jamal, Muhammad Imran Naseer, Zeenat Mirza, Sajjad Karim, Shakeel Ansari, Mourad Assidi, Gauthaman Kalamegam, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Peter Natesan Pushparaj, Mohammed Al-Qahtani P91 Effects of environmental particulate matter on bone-marrow mesenchymal stem cells Muhammad Abu-Elmagd, Gauthaman Kalamegam, Roaa Kadam, Mansour A Alghamdi, Magdy Shamy, Max Costa, Mamdouh I Khoder, Mourad Assidi, Peter Natesan Pushparaj, Mamdooh Gari, Mohammed Al-Qahtani P92 Distinctive charge clusters in human virus proteomes Najla Kharrat, Sabrine Belmabrouk, Rania Abdelhedi, Riadh Benmarzoug, Mourad Assidi, Mohammed H. Al Qahtani, Ahmed Rebai P93 In vitro experimental model and approach in identification of new biomarkers of inflammatory forms of arthritis Ghazi Dhamanhouri, Peter Natesan Pushparaj, Abdelwahab Noorwali, Mohammad Khalid Alwasiyah, Afnan Bahamaid, Saadiah Alfakeeh, Aisha Alyamani, Haneen Alsehli, Mohammed Abbas, Mamdooh Gari, Ali Mobasheri, Gauthaman Kalamegam, Mohammed Al-Qahtani P94 Molecular docking of GABAA receptor subunit γ-2 with novel anti-epileptic compounds Muhammad Faheem, Shilu Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani P95 Breast cancer knowledge, awareness, and practices among Saudi females residing in Jeddah Shilu Mathew, Muhammad Faheem, Shiny Mathew, Peter Natesan Pushparaj, Mohammad H. Al-Qahtani P96 Anti-inflammatory role of Sesamin by Attenuation of Iba1/TNF-α/ICAM-1/iNOS signaling in Diabetic Retinopathy Mohammad Sarwar Jamal, Syed Kashif Zaidi, Raziuddin Khan, Kanchan Bhatia, Mohammed H. Al-Qahtani, Saif Ahmad P97 Identification of drug lead molecule against vp35 protein of Ebola virus: An In-Silico approach Iftikhar AslamTayubi, Manish Tripathi, Syed Asif Hassan, Rahul Shrivastava P98 An approach to personalized medicine from SNP-calling through disease analysis using whole exome-sequencing of three sub-continental populations Iftikhar A Tayubi, Syed Hassan, Hamza A.S Abujabal P99 Low versus high frequency of Glucose –6 – Phosphate Dehydrogenase (G6PD) deficiency in urban against tribal population of Gujarat – A signal to natural selection Ishani Shah, Bushra Jarullah, Mohammad S Jamal, Jummanah Jarullah P100 Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update Ishfaq A Sheikh, Ejaz Ahmad, Mohammad S Jamal, Mohd Rehan, Muhammad Abu-Elmagd, Iftikhar A Tayubi, Samera F AlBasri, Osama S Bajouh, Rola F Turki, Adel M Abuzenadah, Ghazi A Damanhouri, Mohd A Beg, Mohammed Al-Qahtani P101 Prevalence of congenital heart diseases among Down syndrome cases in Saudi Arabia: role of molecular genetics in the pathogenesis Sahar AF Hammoudah, Khalid M AlHarbi, Lama M El-Attar, Ahmed MZ Darwish P102 Combinatorial efficacy of specific pathway inhibitors in breast cancer cells Sara M Ibrahim, Ashraf Dallol, Hani Choudhry, Adel Abuzenadah, Jalaludden Awlia, Adeel Chaudhary, Farid Ahmed, Mohammed Al-Qahtani P103 MiR-143 and miR-145 cluster as potential replacement medicine for the treatment of cancer Mohammad A Jafri, Muhammad Abu-Elmagd, Mourad Assidi, Mohammed Al-Qahtani P104 Metagenomic profile of gut microbiota during pregnancy in Saudi population Imran khan, Muhammad Yasir, Esam I. Azhar, Sameera Al-basri, Elie Barbour, Taha Kumosani P105 Exploration of anticancer targets of selected metabolites of Phoenix dactylifera L. using systems biological approaches Fazal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adel Abuzenada, Taha Abduallah Kumosani, Elie Barbour P106 CD226 and CD40 gene polymorphism in susceptibility to Juvenile rheumatoid arthritis in Egyptian patients Heba M. EL Sayed, Eman A. Hafez P107 Paediatric exome sequencing in autism spectrum disorder ascertained in Saudi families Hans-Juergen Schulten, Aisha Hassan Elaimi, Ibtessam R Hussein, Randa Ibrahim Bassiouni, Mohammad Khalid Alwasiyah, Richard F Wintle, Adeel Chaudhary, Stephen W Scherer, Mohammed Al-Qahtani P108 Crystal structure of the complex formed between Phospholipase A2 and the central core hydrophobic fragment of Alzheimer’s β- amyloid peptide: a reductionist approach Zeenat Mirza, Vikram Gopalakrishna Pillai, Sajjad Karim, Sujata Sharma, Punit Kaur, Alagiri Srinivasan, Tej P Singh, Mohammed Al-Qahtani P109 Differential expression profiling between meningiomas from female and male patients Reem Alotibi, Alaa Al-Ahmadi, Fatima Al-Adwani, Deema Hussein, Sajjad Karim, Mona Al-Sharif, Awatif Jamal, Fahad Al-Ghamdi, Jaudah Al-Maghrabi, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Hans-Juergen Schulten, Mohammed Al-Qahtani P110 Neurospheres as models of early brain development and therapeutics Muhammad Faheem, Peter Natesan Pushparaj, Shilu Mathew, Taha Abdullah Kumosani, Gauthaman Kalamegam, Mohammed Al-Qahtani P111 Identification of a recurrent causative missense mutation p.(W577C) at the LDLR exon 12 in familial hypercholesterolemia affected Saudi families Faisal A Al-Allaf, Zainularifeen Abduljaleel, Abdullah Alashwal, Mohiuddin M. Taher, Abdellatif Bouazzaoui, Halah Abalkhail, Faisal A. Ba-Hammam, Mohammad Athar P112 Epithelial ovarian carcinoma (EOC): Systems oncological approach to identify diagnostic, prognostic and therapeutic biomarkers Gauthaman Kalamegam, Peter Natesan Pushparaj, Muhammad Abu-Elmagd, Farid Ahmed Khalid HussainWali Sait, Nisreen Anfinan, Mamdooh Gari, Adeel Chaudhary, Adel Abuzenadah, Mourad Assidi, Mohammed Al-Qahtani P113 Crohn’s disease phenotype in northern Tunisian population Naira Ben Mami, Yosr Z Haffani, Mouna Medhioub, Lamine Hamzaoui, Ameur Cherif, Msadok Azouz P114 Establishment of In Silico approaches to decipher the potential toxicity and mechanism of action of drug candidates and environmental agents Gauthaman Kalamegam, Fazal Khan, Shilu Mathew, Mohammed Imran Nasser, Mahmood Rasool, Farid Ahmed, Peter Natesan Pushparaj, Mohammed Al-Qahtani P115 1q Gain predicts poor prognosis marker for young breast cancer patients Shereen A Turkistany, Lina M Al-harbi, Ashraf Dallol, Jamal Sabir, Adeel Chaudhary, Adel Abuzenadah P116 Disorders of sex chromosomes in a diagnostic genomic medicine unit in Saudi Arabia: Prevalence, diagnosis and future guidelines Basmah Al-Madoudi, Bayan Al-Aslani, Khulud Al-Harbi, Rwan Al-Jahdali, Hanadi Qudaih, Emad Al Hamzy, Mourad Assidi, Mohammed Al Qahtani P117 Combination of WYE354 and Sunitinib demonstrate synergistic inhibition of acute myeloid leukemia in vitro Asad M Ilyas, Youssri Ahmed, Mamdooh Gari, Farid Ahmed, Mohammed Alqahtani P118 Integrated use of evolutionary information in GWAS reveals important SNPs in Asthma Nada Salem, Sajjad Karim, Elham M Alhathli, Heba Abusamra, Hend F Nour Eldin, Mohammed H Al-Qahtani, Sudhir Kumar P119 Assessment of BRAF, IDH1, IDH2, and EGFR mutations in a series of primary brain tumors Fatima Al-Adwani, Deema Hussein, Mona Al-Sharif, Awatif Jamal, Fahad Al-Ghamdi, Jaudah Al-Maghrabi, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Mohammed Al-Qahtani, Hans-Juergen Schulten P120 Expression profiles distinguish oligodendrogliomas from glioblastoma multiformes with or without oligodendroglioma component Alaa Alamandi, Reem Alotibi, Deema Hussein, Sajjad Karim, Jaudah Al-Maghrabi, Fahad Al-Ghamdi, Awatif Jamal, Saleh S Baeesa, Mohammed Bangash, Adeel Chaudhary, Hans-Juergen Schulten, Mohammed Al-Qahtani P121 Hierarchical clustering in thyroid goiters and hyperplastic lesions Ohoud Subhi, Nadia Bagatian, Sajjad Karim, Adel Al-Johari, Osman Abdel Al-Hamour, Hosam Al-Aradati, Abdulmonem Al-Mutawa, Faisal Al-Mashat, Jaudah Al-Maghrabi, Hans-Juergen Schulten, Mohammad Al-Qahtani P122 Differential expression analysis in thyroiditis and papillary thyroid carcinomas with or without coexisting thyroiditis Nadia Bagatian, Ohoud Subhi, Sajjad Karim, Adel Al-Johari, Osman Abdel Al-Hamour, Abdulmonem Al-Mutawa, Hosam Al-Aradati, Faisal Al-Mashat, Mohammad Al-Qahtani, Hans-Juergen Schulten, Jaudah Al-Maghrabi P123 Metagenomic analysis of waste water microbiome in Sausdi Arabia Muhammad W shah, Muhammad Yasir, Esam I Azhar, Saad Al-Masoodi P124 Molecular characterization of Helicobacter pylori from faecal samples of Tunisian patients with gastric cancer Yosr Z Haffani, Msadok Azouz, Emna Khamla, Chaima Jlassi, Ahmed S. Masmoudi, Ameur Cherif, Lassaad Belbahri P125 Diagnostic application of the oncoscan© panel for the identification of hereditary cancer syndrome Shadi Al-Khayyat, Roba Attas, Atlal Abu-Sanad, Mohammed Abuzinadah, Adnan MerdadAshraf Dallol, Adeel Chaudhary, Mohammed Al-Qahtani, Adel Abuzenadah P126 Characterization of clinical and neurocognitive features in a family with a novel OGT gene missense mutation c. 1193G > A/ (p. Ala319Thr) Habib Bouazzi, Carlos Trujillo, Mohammad Khalid Alwasiyah, Mohammed Al-Qahtani P127 Case report: a rare homozygous deletion mutation of TMEM70 gene associated with 3-Methylglutaconic Aciduria and cataract in a Saudi patient Maha Alotaibi, Rami Nassir P128 Isolation and purification of antimicrobial milk proteins Ishfaq A Sheikh, Mohammad A Kamal, Essam H Jiffri, Ghulam M Ashraf, Mohd A Beg P129 Integrated analysis reveals association of ATP8B1 gene with colorectal cancer Mohammad A Aziz, Rizwan Ali, Mahmood Rasool, Mohammad S Jamal, Nusaibah samman, Ghufrana Abdussami, Sathish Periyasamy, Mohiuddin K Warsi, Mohammed Aldress, Majed Al Otaibi, Zeyad Al Yousef, Mohamed Boudjelal, Abdelbasit Buhmeida, Mohammed H Al-Qahtani, Ibrahim AlAbdulkarim P130 Implication of IL-10 and IL-28 polymorphism with successful anti-HCV therapy and viral clearance Rubi Ghazala, Shilu Mathew, M. Haroon Hamed, Mourad Assidi, Mohammed Al-Qahtani, Ishtiaq Qadri P131 Interactions of endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-2-ethylhexyl phthalate (MEHP) with progesterone receptor Ishfaq A Sheikh, Muhammad Abu-Elmagd, Rola F Turki, Ghazi A Damanhouri, Mohd A. Beg P132 Association of HCV nucleotide polymorphism in the development of hepatocellular carcinoma Mohd Suhail, Abid Qureshi, Adil Jamal, Peter Natesan Pushparaj, Mohammad Al-Qahtani, Ishtiaq Qadri P133 Gene expression profiling by DNA microarrays in colon cancer treated with chelidonine alkaloid Mahmoud Z El-Readi, Safaa Y Eid, Michael Wink P134 Successful in vitro fertilization after eight failed trials Ahmed M. Isa, Lulu Alnuaim, Johara Almutawa, Basim Abu-Rafae, Saleh Alasiri, Saleh Binsaleh P135 Genetic sensitivity analysis using SCGE, cell cycle and mitochondrial membrane potential in OPs stressed leukocytes in Rattus norvegicus through flow cytometric input Nazia Nazam, Mohamad I Lone, Waseem Ahmad, Shakeel A Ansari, Mohamed H Alqahtani
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124. Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation
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Wilson, Catherine H, Crombie, Catriona, Van Der Weyden, Louise, Poulogiannis, George, Rust, Alistair G, Pardo, Mercedes, Gracia, Tannia, Yu, Lu, Choudhary, Jyoti, Poulin, Gino B, McIntyre, Rebecca E, Winton, Douglas J, March, H Nikki, Arends, Mark J, Fraser, Andrew G, and Adams, David J
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Male ,Stem Cells ,Tumor Suppressor Proteins ,Intracellular Signaling Peptides and Proteins ,Ubiquitination ,Vesicular Transport Proteins ,Receptors, Cytoplasmic and Nuclear ,Cell Differentiation ,Prognosis ,3. Good health ,DNA-Binding Proteins ,Intestines ,Mice ,Cell Transformation, Neoplastic ,Neoplasms ,Animals ,Homeostasis ,Humans ,Female ,Carrier Proteins ,Oxidoreductases ,Gene Deletion ,Cell Proliferation ,Transcription Factors - Abstract
Genetic screens in simple model organisms have identified many of the key components of the conserved signal transduction pathways that are oncogenic when misregulated. Here, we identify H37N21.1 as a gene that regulates vulval induction in let-60(n1046gf), a strain with a gain-of-function mutation in the Caenorhabditis elegans Ras orthologue, and show that somatic deletion of Nrbp1, the mouse orthologue of this gene, results in an intestinal progenitor cell phenotype that leads to profound changes in the proliferation and differentiation of all intestinal cell lineages. We show that Nrbp1 interacts with key components of the ubiquitination machinery and that loss of Nrbp1 in the intestine results in the accumulation of Sall4, a key mediator of stem cell fate, and of Tsc22d2. We also reveal that somatic loss of Nrbp1 results in tumourigenesis, with haematological and intestinal tumours predominating, and that nuclear receptor binding protein 1 (NRBP1) is downregulated in a range of human tumours, where low expression correlates with a poor prognosis. Thus NRBP1 is a conserved regulator of cell fate, that plays an important role in tumour suppression.
125. A Genome-Wide Association Study for Regulators of Micronucleus Formation in Mice
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McIntyre, Rebecca E, Nicod, Jérôme, Robles-Espinoza, Carla Daniela, Maciejowski, John, Cai, Na, Hill, Jennifer, Verstraten, Ruth, Iyer, Vivek, Rust, Alistair G, Balmus, Gabriel, Mott, Richard, Flint, Jonathan, and Adams, David J
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Male ,Sex Characteristics ,Genotype ,Quantitative Trait Loci ,Chromosome Mapping ,Chromosome Breakage ,Micronuclei ,genome-wide association study (GWAS) ,genomic instability ,Polymorphism, Single Nucleotide ,3. Good health ,Outbred mice ,Mice ,Phenotype ,Animals ,Female ,genetic mapping ,Micronuclei, Chromosome-Defective ,Genome-Wide Association Study - Abstract
In mammals the regulation of genomic instability plays a key role in tumor suppression and also controls genome plasticity, which is important for recombination during the processes of immunity and meiosis. Most studies to identify regulators of genomic instability have been performed in cells in culture or in systems that report on gross rearrangements of the genome, yet subtle differences in the level of genomic instability can contribute to whole organism phenotypes such as tumor predisposition. Here we performed a genome-wide association study in a population of 1379 outbred Crl:CFW(SW)-US_P08 mice to dissect the genetic landscape of micronucleus formation, a biomarker of chromosomal breaks, whole chromosome loss, and extranuclear DNA. Variation in micronucleus levels is a complex trait with a genome-wide heritability of 53.1%. We identify seven loci influencing micronucleus formation (false discovery rate
126. Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia.
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van der Weyden, Louise, Giotopoulos, George, Wong, Kim, Rust, Alistair G, Robles-Espinoza, Carla Daniela, Osaki, Hikari, Huntly, Brian J, and Adams, David J
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Background: B-cell precursor acute lymphoblastic leukemia (B-ALL) is amongst the leading causes of childhood cancer-related mortality. Its most common chromosomal aberration is the ETV6-RUNX1 fusion gene, with ~25% of ETV6-RUNX1 patients also carrying PAX5 alterations.Methods: We have recreated this mutation background by inter-crossing Etv6-RUNX1 (Etv6 (RUNX1-SB)) and Pax5(+/-) mice and performed an in vivo analysis to find driver genes using Sleeping Beauty transposon-mediated mutagenesis and also exome sequencing.Results: Combination of Etv6-RUNX1 and Pax5(+/-) alleles generated a transplantable B220 + CD19+ B-ALL with a significant disease incidence. RNA-seq analysis showed a gene expression pattern consistent with arrest at the pre-B stage. Analysis of the transposon common insertion sites identified genes involved in B-cell development (Zfp423) and the JAK/STAT signaling pathway (Jak1, Stat5 and Il2rb), while exome sequencing revealed somatic hotspot mutations in Jak1 and Jak3 at residues analogous to those mutated in human leukemias, and also mutation of Trp53.Conclusions: Powerful synergies exists in our model suggesting STAT pathway activation and mutation of Trp53 are potent drivers of B-ALL in the context of Etv6-RUNX1;Pax5(+/-). [ABSTRACT FROM AUTHOR]- Published
- 2015
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127. Corrigendum: The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma.
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Pérez-Mancera, Pedro A., Rust, Alistair G., van der Weyden, Louise, Kristiansen, Glen, Li, Allen, Sarver, Aaron L., Silverstein, Kevin A. T., Grützmann, Robert, Aust, Daniela, Rümmele, Petra, Knösel, Thomas, Herd, Colin, Stemple, Derek L., Kettleborough, Ross, Brosnan, Jacqueline A., Li, Ang, Morgan, Richard, Knight, Spencer, Yu, Jun, and Stegeman, Shane
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ADENOCARCINOMA - Abstract
A correction to the article "The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma" that was published in the 2012 issue is presented.
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- 2013
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128. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4.
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Gilchrist, Mark, Thorsson, Vesteinn, Li, Bin, Rust, Alistair G., Korb, Martin, Roach, Jared C., Kennedy, Kathleen, Hai, Tsonwin, Bolouri, Hamid, and Aderem, Alan
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BIOLOGY - Abstract
A correction to the article "Systems Biology Approaches Identify ATF3 as a Negative Regulator of Toll-like Receptor 4," by Mark Gilchrist and colleagues that was published in a 2006 issue is presented.
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- 2008
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129. Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.
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Rangel, Roberto, Guzman-Rojas, Liliana, Mann, Michael B., Newberg, Justin Y., Takahiro Kodama, Jenkins, Nancy A., Copeland, Neal G., Song-Choon Lee, Ward, Jerrold M., Chin, Kuan-Yew, Hon-Kim Ban, Kenneth, McNoe, Leslie A., Selvanesan, Luxmanan, Black, Michael A., and Rust, Alistair G.
- Subjects
- *
TRANSPOSONS , *MUTAGENESIS , *GENES , *BREAST cancer research , *PTEN protein - Abstract
Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
130. The mutational landscapes of genetic and chemical models of Kras-driven lung cancer.
- Author
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Westcott, Peter M. K., Halliwill, Kyle D., To, Minh D., Rashid, Mamunur, Rust, Alistair G., Keane, Thomas M., Delrosario, Reyno, Jen, Kuang-Yu, Gurley, Kay E., Kemp, Christopher J., Fredlund, Erik, Quigley, David A., Adams, David J., and Balmain, Allan
- Subjects
- *
TUMORS , *NEOPLASTIC cell transformation , *NON-small-cell lung carcinoma , *CARCINOMA , *CANCER - Abstract
Next-generation sequencing of human tumours has refined our understanding of the mutational processes operative in cancer initiation and progression, yet major questions remain regarding the factors that induce driver mutations and the processes that shape mutation selection during tumorigenesis. Here we performed whole-exome sequencing on adenomas from three mouse models of non-small-cell lung cancer, which were induced either by exposure to carcinogens (methyl-nitrosourea (MNU) and urethane) or by genetic activation of Kras (KrasLA2). Although the MNU-induced tumours carried exactly the same initiating mutation in Kras as seen in the KrasLA2 model (G12D), MNU tumours had an average of 192 non-synonymous, somatic single-nucleotide variants, compared with only six in tumours from the KrasLA2 model. By contrast, the KrasLA2 tumours exhibited a significantly higher level of aneuploidy and copy number alterations compared with the carcinogen-induced tumours, suggesting that carcinogen-induced and genetically engineered models lead to tumour development through different routes. The wild-type allele of Kras has been shown to act as a tumour suppressor in mouse models of non-small-cell lung cancer. We demonstrate that urethane-induced tumours from wild-type mice carry mostly (94%) Kras Q61R mutations, whereas those from Kras heterozygous animals carry mostly (92%) Kras Q61L mutations, indicating a major role for germline Kras status in mutation selection during initiation. The exome-wide mutation spectra in carcinogen-induced tumours overwhelmingly display signatures of the initiating carcinogen, while adenocarcinomas acquire additional C > T mutations at CpG sites. These data provide a basis for understanding results from human tumour genome sequencing, which has identified two broad categories of tumours based on the relative frequency of single-nucleotide variations and copy number alterations, and underline the importance of carcinogen models for understanding the complex mutation spectra seen in human cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
131. Identification of FoxR2 as an Oncogene in Medulloblastoma.
- Author
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Hideto Koso, Asano Tsuhako, Lyons, Eli, Ward, Jerrold M., Rust, Alistair G., Adams, David J., Jenkins, Nancy A., Copeland, Neal G., and Sumiko Watanabe
- Subjects
- *
MEDULLOBLASTOMA , *BRAIN tumors , *NEURONS , *MUTAGENESIS , *TRANSCRIPTION factors , *ONCOGENES , *CELL proliferation , *BINDING sites - Abstract
Medulloblastoma is the most common pediatric brain tumor, and in ~25% of cases, it is driven by aberrant activation of the Sonic Hedgehog (SHH) pathway in granule neuron precursor (GNP) cells. In this study, we identified novel medulloblastoma driver genes through a transposon mutagenesis screen in the developing brain of wild-type and Trp53 mutant mice. Twenty-six candidates were identified along with established driver genes such as Gli1 and Crebbp. The transcription factor FoxR2, the most frequent gene identified in the screen, is overexpressed in a small subset of human medulloblastoma of the SHH subtype. Tgif2 and Alx4, 2 new putative oncogenes identified in the screen, are strongly expressed in the SHH subtype of human medulloblastoma. Mutations in these two genes were mutually exclusive with mutations in Gli1 and tended to cooccur, consistent with involvement in the SHH pathway. Notably, Foxr2, Tgif2, and Alx4 activated Gli-binding sites in cooperation with Gli1, strengthening evidence that they function in SHH signaling. In support of an oncogenic function, Foxr2 overexpression transformed NIH3T3 cells and promoted proliferation of GNPs, the latter of which was also observed for Tgif2 and Alx4. These findings offer forward genetic and functional evidence associating Foxr2, Tgif2, and Alx4 with SHH subtype medulloblastoma. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
132. A Genomic Regulatory Network for Development.
- Author
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Davidson, Eric H., Rast, Jonathan P., Oliveri, Paola, Ransick, Andrew, Calestani, Cristina, Chiou-Hwa Yuh, Minokawa, Takuya, Amore, Gabriele, Hinman, Veronica, Arenas-Mena, César, Otim, Ochan, Brown, C. Titus, Livi, Carolina B., Pei Yun Lee, Revilla, Roger, Rust, Alistair G., Zheng jun Pan, Schilstra, Maria J., Clarke, Peter J.C., and Arnone, Maria I.
- Subjects
- *
SEA urchin embryos , *BIOLOGY , *GENETICS - Abstract
Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
133. Identification of genes that promote PI3K pathway activation and prostate tumour formation.
- Author
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Francis JC, Capper A, Rust AG, Ferro K, Ning J, Yuan W, de Bono J, Pettitt SJ, and Swain A
- Subjects
- Male, Humans, Animals, Mice, Organoids metabolism, Organoids pathology, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-akt genetics, Cell Line, Tumor, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Prostatic Neoplasms metabolism, Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol 3-Kinases genetics, Peptide Initiation Factors genetics, Peptide Initiation Factors metabolism, Signal Transduction genetics, Eukaryotic Translation Initiation Factor 5A, PTEN Phosphohydrolase genetics, PTEN Phosphohydrolase metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism
- Abstract
We have performed a functional in vivo mutagenesis screen to identify genes that, when altered, cooperate with a heterozygous Pten mutation to promote prostate tumour formation. Two genes, Bzw2 and Eif5a2, which have been implicated in the process of protein translation, were selected for further validation. Using prostate organoid models, we show that either Bzw2 downregulation or EIF5A2 overexpression leads to increased organoid size and in vivo prostate growth. We show that both genes impact the PI3K pathway and drive a sustained increase in phospho-AKT expression, with PTEN protein levels reduced in both models. Mechanistic studies reveal that EIF5A2 is directly implicated in PTEN protein translation. Analysis of patient datasets identified EIF5A2 amplifications in many types of human cancer, including the prostate. Human prostate cancer samples in two independent cohorts showed a correlation between increased levels of EIF5A2 and upregulation of a PI3K pathway gene signature. Consistent with this, organoids with high levels of EIF5A2 were sensitive to AKT inhibitors. Our study identified novel genes that promote prostate cancer formation through upregulation of the PI3K pathway, predicting a strategy to treat patients with genetic aberrations in these genes particularly relevant for EIF5A2 amplified tumours., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
134. Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.
- Author
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Vaishnavi A, Juan J, Jacob M, Stehn C, Gardner EE, Scherzer MT, Schuman S, Van Veen JE, Murphy B, Hackett CS, Dupuy AJ, Chmura SA, van der Weyden L, Newberg JY, Liu A, Mann K, Rust AG, Weiss WA, Kinsey CG, Adams DJ, Grossmann A, Mann MB, and McMahon M
- Subjects
- Animals, Humans, Mice, Cell Proliferation, Lung pathology, Mutagenesis, Wnt Signaling Pathway, Adenocarcinoma of Lung genetics, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics, Proto-Oncogene Proteins B-raf metabolism, RNA-Binding Proteins genetics, Trans-Activators metabolism, Carcinogenesis genetics
- Abstract
Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/β-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression., Significance: Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease., (©2022 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2022
- Full Text
- View/download PDF
135. Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
- Author
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Wagner S, Vlachogiannis G, De Haven Brandon A, Valenti M, Box G, Jenkins L, Mancusi C, Self A, Manodoro F, Assiotis I, Robinson P, Chauhan R, Rust AG, Matthews N, Eason K, Khan K, Starling N, Cunningham D, Sadanandam A, Isacke CM, Kirkin V, Valeri N, and Whittaker SR
- Subjects
- Animals, Azepines pharmacology, Cell Line, Tumor, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Drug Synergism, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Mutation, Organoids drug effects, Proto-Oncogene Proteins p21(ras) genetics, Pyridones pharmacology, Pyrimidinones pharmacology, Triazoles pharmacology, Xenograft Model Antitumor Assays, Azepines administration & dosage, Colorectal Neoplasms drug therapy, Drug Resistance, Neoplasm drug effects, Gene Regulatory Networks drug effects, Interferons metabolism, Pyridones administration & dosage, Pyrimidinones administration & dosage, Triazoles administration & dosage
- Abstract
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed a pharmacogenomic analysis of MEKi-sensitive versus MEKi-resistant colorectal cancer cell lines. Strikingly, interferon- and inflammatory-related gene sets were enriched in cell lines exhibiting intrinsic and acquired resistance to MEK inhibition. The bromodomain inhibitor JQ1 suppressed interferon-stimulated gene (ISG) expression and in combination with MEK inhibitors displayed synergistic effects and induced apoptosis in MEKi-resistant colorectal cancer cell lines. ISG expression was confirmed in patient-derived organoid models, which displayed resistance to trametinib and were resensitized by JQ1 co-treatment. In in vivo models of colorectal cancer, combination treatment significantly suppressed tumor growth. Our findings provide a novel explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, known for its inflammatory nature. Moreover, the high expression of ISGs was associated with significantly reduced survival of colorectal cancer patients. Excitingly, we have identified novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer.
- Published
- 2019
- Full Text
- View/download PDF
136. Improving computational predictions of cis-regulatory binding sites.
- Author
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Robinson M, Sun Y, Boekhorst RT, Kaye P, Adams R, Davey N, and Rust AG
- Subjects
- Artificial Intelligence, Binding Sites genetics, Computational Biology, Databases, Protein, Gene Expression Regulation, Genomics statistics & numerical data, Proteomics statistics & numerical data, Algorithms, DNA genetics, DNA metabolism
- Abstract
The location of cis-regulatory binding sites determine the connectivity of genetic regulatory networks and therefore constitute a natural focal point for research into the many biological systems controlled by such regulatory networks. Accurate computational prediction of these binding sites would facilitate research into a multitude of key areas, including embryonic development, evolution, pharmacogenemics, cancer and many other transcriptional diseases, and is likely to be an important precursor for the reverse engineering of genome wide, genetic regulatory networks. Many algorithmic strategies have been developed for the computational prediction of cis-regulatory binding sites but currently all approaches are prone to high rates of false positive predictions, and many are highly dependent on additional information, limiting their usefulness as research tools. In this paper we present an approach for improving the accuracy of a selection of established prediction algorithms. Firstly, it is shown that species specific optimization of algorithmic parameters can, in some cases, significantly improve the accuracy of algorithmic predictions. Secondly, it is demonstrated that the use of non-linear classification algorithms to integrate predictions from multiple sources can result in more accurate predictions. Finally, it is shown that further improvements in prediction accuracy can be gained with the use of biologically inspired post-processing of predictions.
- Published
- 2006
137. Initial sequencing and comparative analysis of the mouse genome.
- Author
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Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Emes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigó R, Guyer M, Hardison RC, Haussler D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mott R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O'Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tesler G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, and Lander ES
- Subjects
- Animals, Base Composition, Conserved Sequence genetics, CpG Islands genetics, Gene Expression Regulation, Genes genetics, Genetic Variation genetics, Genome, Human, Genomics, Humans, Mice classification, Mice, Knockout, Mice, Transgenic, Models, Animal, Multigene Family genetics, Mutagenesis, Neoplasms genetics, Proteome genetics, Pseudogenes genetics, Quantitative Trait Loci genetics, RNA, Untranslated genetics, Repetitive Sequences, Nucleic Acid genetics, Selection, Genetic, Sequence Analysis, DNA, Sex Chromosomes genetics, Species Specificity, Synteny, Chromosomes, Mammalian genetics, Evolution, Molecular, Genome, Mice genetics, Physical Chromosome Mapping
- Abstract
The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.
- Published
- 2002
- Full Text
- View/download PDF
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