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C-Terminal-Truncating ASXL1 Mutations Induce MDS Via Inhibition Of PRC2

BLOOD 2013年第21期122卷 471-471页

作者： Inoue, Daichi Kitaura, Jiro Togami, Katsuhiro Nishimura, Koutarou Enomoto, Yutaka Uchida, Tomoyuki Kagiyama, Yuki Kawabata, Kimihito Cojin Nakahara, Fumio Oki, Toshihiko Harada, Hironori Ochiya, Takahiro Aburatani, Hiroyuki Kimura, Hiroshi Thol, Felicitas Heuser, Michael Levine, Ross L. Abdel-Wahab, Omar Kitamura, Toshio Division of Cellular Therapy The Institute of Medical Science The University of Tokyo Tokyo Japan Division of Hematological Malignancy National Cancer Center Research Institute Tokyo Japan Department of Hematology Juntendo University School of Medicine Tokyo Japan Sec. Meta. National Cancer Center Research Institute Tokyo Japan Genome Science Division Research Center for Advanced Science and Technology The University of Tokyo Tokyo Japan Graduate School of Frontier Biosciences Osaka University Suita Japan Department of Hematology Hemostasis Oncology and Stem Cell Transplantation Hannover Medical School Hannover Germany Department of Medicine Memorial Sloan-Kettering Cancer Center New York NY USA Leukemia Service and Human Oncology and Pathogenesis Program Memorial Sloan-Kettering Cancer Center New York City NY USA

Recurrent mutations of ASXL1 (Additional sex combs-like1) are found in various hematological malignancies including myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia, and acute myeloid leukemia (AML) with myelodysplasia-related changes. Additionally, ASXL1 mutations are linked with adverse survival in a variety of myeloid malignancies. A previous study demonstrated that loss of ASXL1 in mice promotes myeloid transformation by impairing polycomb repressive complex 2 (PRC2)-mediated gene repression at a number of critical loci and leads to myeloid transformation. However, most ASXL1 mutations are heterozygous and located in the 5' region of the last exon, indicating a dominant-negative or gain-of-function feature of a truncated ASXL1 protein. Therefore, we investigated if the C-terminal truncated form of ASXL1 (ASXL1-MT) contributes to the development of myeloid malignancies. To this end, we examined the effects of ASXL1-MT using in vitro and in vivo experiments. In in vitro experiment, expression of ASXL1-MT inhibited G-CSF-induced myeloid differentiation of 32Dcl3 cells. In a mouse bone marrow transplantation (BMT) model, ASXL1-MT induced multilineage dysplasia, differentiation block, slowly progressive pancytopenia, BM hyperplasia and splenomegaly. The transduced mice died of severe anemia after a long latency (median survival, 400.5 days), and some of the mice progressed to overt leukemia. Thus, the current model displays all of the features of human MDS. In addition, ASXL1-MT collaborated with N-RAS-G12V, which confers a proliferative advantage, in inducing progression of N-RAS-G12V-induced myeloproliferative neoplasm (MPN) to AML, suggesting that ASXL1-MT contributes to leukemic transformation by inhibiting differentiation of MPN cells. To clarify the molecular mechanism for differentiation block and MDS development induced by ASXL1-MT, we performed expression profiles of 32Dcl3 cells transduced with ASXL1-MT and BM cells of the MDS mice. Of not

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Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women

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Human molecular genetics 2016年第3期25卷 620-9页

作者： Zhaoming Wang Wei Jie Seow Kouya Shiraishi Chao A Hsiung Keitaro Matsuo Jie Liu Kexin Chen Taiki Yamji Yang Yang I-Shou Chang Chen Wu Yun-Chul Hong Laurie Burdett Kathleen Wyatt Charles C Chung Shengchao A Li Meredith Yeager Amy Hutchinson Wei Hu Neil Caporaso Maria T Landi Nilanjan Chatterjee Minsun Song Joseph F Fraumeni Takashi Kohno Jun Yokota Hideo Kunitoh Kyota Ashikawa Yukihide Momozawa Yataro Daigo Tetsuya Mitsudomi Yasushi Yatabe Toyoaki Hida Zhibin Hu Juncheng Dai Hongxia Ma Guangfu Jin Bao Song Zhehai Wang Sensen Cheng Zhihua Yin Xuelian Li Yangwu Ren Peng Guan Jiang Chang Wen Tan Chien-Jen Chen Gee-Chen Chang Ying-Huang Tsai Wu-Chou Su Kuan-Yu Chen Ming-Shyan Huang Yuh-Min Chen Hong Zheng Haixin Li Ping Cui Huan Guo Ping Xu Li Liu Motoki Iwasaki Taichi Shimazu Shoichiro Tsugane Junjie Zhu Gening Jiang Ke Fei Jae Yong Park Yeul Hong Kim Jae Sook Sung Kyong Hwa Park Young Tae Kim Yoo Jin Jung Chang Hyun Kang In Kyu Park Hee Nam Kim Hyo-Sung Jeon Jin Eun Choi Yi Young Choi Jin Hee Kim In-Jae Oh Young-Chul Kim Sook Whan Sung Jun Suk Kim Ho-Il Yoon Sun-Seog Kweon Min-Ho Shin Adeline Seow Ying Chen Wei-Yen Lim Jianjun Liu Maria Pik Wong Victor Ho Fun Lee Bryan A Bassig Margaret Tucker Sonja I Berndt Wong-Ho Chow Bu-Tian Ji Junwen Wang Jun Xu Alan Dart Loon Sihoe James C M Ho John K C Chan Jiu-Cun Wang Daru Lu Xueying Zhao Zhenhong Zhao Junjie Wu Hongyan Chen Li Jin Fusheng Wei Guoping Wu She-Juan An Xu-Chao Zhang Jian Su Yi-Long Wu Yu-Tang Gao Yong-Bing Xiang Xingzhou He Jihua Li Wei Zheng Xiao-Ou Shu Qiuyin Cai Robert Klein William Pao Charles Lawrence H Dean Hosgood Chin-Fu Hsiao Li-Hsin Chien Ying-Hsiang Chen Chung-Hsing Chen Wen-Chang Wang Chih-Yi Chen Chih-Liang Wang Chong-Jen Yu Hui-Ling Chen Yu-Chun Su Fang-Yu Tsai Yi-Song Chen Yao-Jen Li Tsung-Ying Yang Chien-Chung Lin Pan-Chyr Yang Tangchun Wu Dongxin Lin Baosen Zhou Jinming Yu Hongbing Shen Michiaki Kubo Stephen J Chanock Nathaniel Rothman Qing Lan Cancer Genomics Research Laboratory Leidos Biomedical Research Inc. Gaithersburg MD USA Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA wangzha@mail.nih.gov. Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA. Division of Genome Biology National Cancer Center Hospital Tokyo Japan. Institute of Population Health Sciences. Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan. Department of Oncology Shandong Cancer Hospital and Institute Shandong Academy of Medical Sciences Jinan China. Department of Epidemiology and Biostatistics National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin China. Epidemiology and Prevention Group Research Center for Cancer Prevention and Screening National Cancer Center Tokyo Japan. Shanghai Pulmonary Hospital Shanghai China. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. Department of Preventive Medicine. Cancer Genomics Research Laboratory Leidos Biomedical Research Inc. Gaithersburg MD USA Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA. Cancer Genome Biology Group Institute of Predictive and Personalized Medicine of Cancer Barcelona Spain. Department of Medical Oncology Japanese Red Cross Medical Center Tokyo Japan. Laboratory for Genotyping Development RIKEN Center for Integrative Medical Sciences Yokohama Japan. Laboratory of Molecular Medicine Human Genome Center Institute of Medical Science University of Tokyo Tokyo Japan. Division of Thoracic Surgery Kinki University School of Medicine

genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.

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Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015) : Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015

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BMC genomics 2016年第6期17 Suppl 6卷 487页

作者： Jerry W. Shay Noriko Homma Ruyun Zhou Muhammad Imran Naseer Adeel G. Chaudhary Mohammed Al-Qahtani Nobutaka Hirokawa Maryam Goudarzi Albert J. Fornace 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 Heba Alkhatabi Anne Goodeve Laura Crookes Nikolas Niksic Nicholas Beauchamp Adel M. Abuzenadah Jim Vaught Bruce Budowle Mourad Assidi Abdelbaset Buhmeida Leena Merdad Sudhir Kumar Sayaka Miura Karen Gomez Mahmood Rasool Ahmed Rebai Sajjad Karim Hend F. Nour Eldin Heba Abusamra Elham M. Alhathli Nada Salem Mohammed H. Al-Qahtani Hossam Faheem Ashok Agarwa Eberhard Nieschlag Joachim Wistuba Oliver S. Damm Mohd A. Beg Taha A. Abdel-Meguid Hisham A. Mosli Osama S. Bajouh Serdar Coskun Muhammad Abu-Elmagd Ashraf Dallol Sahar Hakamy Wejdan Al-Qahtani Asia Al-Harbi Shireen Hussain Burak Ozkosem Rick DuBois Safia S. Messaoudi Maryam T. Dandana Touhami Mahjoub Wassim Y. Almawi S. Abdalla M. Nabil Al-Aama 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 Sajid Mehmood Naeem Mahmood Ashraf Awais Asif Muhammad Bilal Malik Siddique Mehmood Aadil Hussain Qazi Mohammad Sajid Jamal Mughees Uddin Siddiqui Mohammad A. Alzohairy Mohammad A. Al Karaawi Taoufik Nedjadi Heba Al-Khattabi Adel Al-Ammari Ahmed Al-Sayyad Hédia Zitouni Nozha Raguema Marwa Ben Ali Wided Malah Raja Lfalah Wassim Almawi Mohammed Elanbari Andrey Ptitsyn Sana Mahjoub Rabeb El Ghali Bechir Achour Nidhal Ben Amor Brahim N’siri Hamid Morjani Esam Azhar Vera Chayeb Maryam Dendena Hedia Zitouni Khedija Zouari-Limayem Bassem Refaat Ahmed M. Ashshi Sarah A. Batwa Hazem Ramadan Amal Awad Ahmed Ateya Adel Galal Ahmed El-Shemi Ahmad Ashshi Mohammed Basalamah Youjin Na Cha University of Texas Southwestern Medical Center Dallas USA Department of Cell Biology and Anatomy Graduate School of Medicine the University of Tokyo Tokyo Japan Center of Excellence in Genomic Medicine Research King Abdulaziz University Jeddah Saudi Arabia Department of Biochemistry and Molecular & Cellular Biology Lombardi Comprehensive Cancer Center Georgetown University Washington USA Department of Oncology Lombardi Comprehensive Cancer Center Georgetown University Washington USA Department of Radiation Medicine Lombardi Comprehensive Cancer Center Georgetown University Washington USA Center of Excellence in Genomic Medicine Research (CEGMR) King Abdulaziz University Jeddah Kingdom of Saudi Arabia King Fahd Medical Research Centre King Abdulaziz University Jeddah Saudi Arabia Centre of Excellence in Genomic Medicine Research King Abdulaziz University Jeddah Saudi Arabia Sheffield Diagnostic Genetic Service Sheffield Children’s NHS Foundation Trust Western Bank Sheffield UK Center of Innovations in Personalized Medicine King Abdulaziz University Jeddah Saudi Arabia President ISBER Editor-in-Chief Biopreservation & Biobanking ᅟ USA Institute of Applied Genetics Department of Molecular and Medical Genetics University of North Texas Health Science Center Fort Worth USA Department of Dental Public Health Faculty of Dentistry King Abdulaziz University Jeddah Saudi Arabia Institute for Genomics and Evolutionary Medicine Temple University Philadelphia USA Center of Excellence in Genomic Medicine King Abdulaziz University Jeddah Kingdom of Saudi Arabia Laboratory of Molecular and Cellular Screening Processes (Bioinformatics Group) Centre of Biotechnology of Sfax Sfax Tunisia Fujitsu Technology Solutions International ᅟ ᅟ Case Western Reserve University School of Medicine and Lerner College of Medicine Cleveland Clinic Foundation Cleveland USA American Center for Reproductive Medicine Andrology Center Cleveland USA Center for Reproductive Medicine and

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 me

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31st Annual Meeting and Associated programs of the Society for Immunotherapy of Cancer (SITC 2016): part two Abstracts

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JOURNAL FOR IMMUNOTHERAPY OF CANCER 2016年第SUPPL 1期4卷 107-221页

作者： [Anonymous] Department of Immunology University of Texas MD Anderson Cancer Center Houston TX USA Department of Cancer Medicine University of Texas MD Anderson Cancer Center Houston TX USA Immune Design Seattle WA USA Innate Pharma Marseille Provence-Alpes-Cote d’Azur France MedImmune Cambridge England UK Georgetown-Lombardi Comprehensive Cancer Center Washington DC USA Westmead and Blacktown Hospitals Melanoma Institute Australia and the University of Sydney Westmead New South Wales Australia University of California Los Angeles CA USA University of Washington Seattle WA USA Dana-Farber Cancer Institute/Brigham and Women’s Hospital Harvard University Boston MA USA University of Texas MD Anderson Cancer Center Houston TX USA Beth Israel Deaconess Medical Center Boston MA USA Gallipoli Medical Research Foundation Greenslopes Private Hospital and the University of Queensland Greenslopes Queensland Australia Olivia Newton-John Cancer Research Institute Heidelberg Victoria Australia Canterbury District Health Board Christchurch Hospital Christchurch New Zealand Waikato Hospital Regional Cancer Centre Hamilton New Zealand Royal Prince Alfred Hospital Melanoma Institute Australia the University of Sydney and Chris O’Brien Lifehouse Camperdown New South Wales Australia Tasman Oncology Research Southport Gold Coast Queensland Australia Merck & Co. Inc. Kenilworth NJ USA Quantitative Solutions A Certara Company Oss Netherlands Melanoma Institute Australia the University of Sydney Mater Hospital and Royal North Shore Hospital Wollstonecraft New South Wales Australia Columbia University Medical Center New York NY USA Institut d’Investigacions Biomediques August Pi i Sunyer Barcelona Catalonia Spain Icahn School of Medicine at Mount Sinai New York NY USA New York Presbyterian/Columbia University Medical Center New York NY USA Memorial Sloan Kettering Cancer Center New York NY USA Peregrine Pharmaceuticals Inc. Tustin CA USA Regeneron Tarrytown NY USA University of

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Research Highlights: Shear-activated nanotherapeutics

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Nanomedicine 2012年第11期7卷 1653-1655页

作者： Sukanya Iyer Mitchel J Doktycz Graduate Program in Genome Science & Technology University of Tennessee Knoxville TN 37996 USA Biosciences Division Oak Ridge National Laboratory Oak Ridge TN 37831 USA Center for Nanophase Materials Sciences Oak Ridge National Laboratory Oak Ridge TN 37831 USA.

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Building better interdisciplinary scientists: creating graduate level courses to address the communication gap in interdisciplinary research

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BMC Bioinformatics 2012年第12期13卷 1-2页

作者： Denise R Koessler Elizabeth G Johnson Jordan M Utley Harry A Richards Cynthia B Peterson Department of Electrical Engineering and Computer Science The University of Tennessee Knoxville TN 37996 USA Department of Microbiology The University of Tennessee Knoxville TN 37996 USA UT/ORNL Graduate School of Genome Science and Technology The University of Tennessee Knoxville TN 37996 USA SCALE-IT Program Administrator The University of Tennessee Knoxville TN 37996 USA Department of Biochemistry and Molecular Biology The University of Tennessee Knoxville TN 37996 USA

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Enhanced Heliothis virescens midgut regeneration and its role in resistance to Bacillus thuringiensis toxins

Enhanced Heliothis virescens midgut regeneration and its rol...

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第2届昆虫中肠生物学国际研讨会

作者： Ana(i)s S.Castagnola Omaththage P.Perera Cris Oppert Jerreme Jackson Fred Gould Juan Luis Jurat-Fuentes Department of Entomology and Plant Pathology University of TennesseeKnoxvilleTN 37996USA Southern Insect Management Research UnitUSDA-ARSStonevilleMS 38776USA Genome Science and Technology Graduate ProgramUniversity of TennesseeKnoxvilleTN 37996 Department of EntomologyNorth Carolina State UniversityRaleigh 27607USA

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Model for biological communication in a nanofabricated cell-mimic driven by stochastic resonance

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Nano Communication Networks 2011年第1期2卷 39-49页

作者： Karig, David K. Siuti, Piro Dar, Roy D. Retterer, Scott T. Doktycz, Mitchel J. Simpson, Michael L. Center for Nanophase Materials Sciences Oak Ridge National Laboratory Bethel Valley Road Oak Ridge TN 37831 United States Biosciences Division Oak Ridge National Laboratory Oak Ridge TN 37831 United States Graduate Program in Genome Science and Technology University of Tennessee Knoxville TN 37996 United States Department of Physics and Astronomy University of Tennessee Knoxville TN 37996-2010 United States Department of Materials Science and Engineering University of Tennessee Knoxville TN 37996-2010 United States Center for Environmental Biotechnology University of Tennessee Knoxville TN 37996-2010 United States

Cells offer natural examples of highly efficient networks of nanomachines. Accordingly, both intracellular and intercellular communication mechanisms in nature are looked to as a source of inspiration and instruction for engineered nanocommunication. Harnessing biological functionality in this manner requires an interdisciplinary approach that integrates systems biology, synthetic biology, and nanofabrication. Here, we present a model system that exemplifies the synergism between these realms of research. We propose a synthetic gene network for operation in a nanofabricated cell mimic array that propagates a biomolecular signal over long distances using the phenomenon of stochastic resonance. Our system consists of a bacterial quorum sensing signal molecule, a bistable genetic switch triggered by this signal, and an array of nanofabricated cell mimic wells that contain the genetic system. An optimal level of noise in the system helps to propagate a time-varying AHL signal over long distances through the array of mimics. This noise level is determined both by the system volume and by the parameters of the genetic network. Our proposed genetically driven stochastic resonance system serves as a testbed for exploring the potential harnessing of gene expression noise to aid in the transmission of a time-varying molecular signal. © 2011.

关键词： Gene expression

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Using a literature-based NMF model for discovering gene functional relationships

Using a literature-based NMF model for discovering gene func...

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IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW)

作者： Elina Tjioe Michael Berry Ramin Homayouni Genome Science and Technology Graduate School University of Tennessee Knoxville TN USA Department of Electrical Engineering and Computer Science University of Tennessee Knoxville TN USA Bioinformatics Program Department of Biology University of Memphis Memphis TN USA

The rapid growth of the biomedical literature and genomic information presents a major challenge for determining the functional relationships among genes. In this study, we develop a Web-based bioinformatics software environment called FAUN or feature annotation using nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. We tested FAUN on three manually constructed gene document collections, and then used it to analyze several microarray-derived gene sets obtained from studies of the developing cerebellum in normal and mutant mice. FAUN provides utilities for collaborative knowledge discovery and identification of new gene relationships from text streams and repositories (e.g., MEDLINE). It is particularly useful for the validation and analysis of gene associations suggested by microarray experimentation.

关键词： Bioinformatics Genomics Data mining Matrix decomposition Large scale integration Feature extraction Iterative methods Biological system modeling Computer science Computational biology

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