-OMICS AND PROGNOSTIC MARKERS

Neuro-Oncology, Nov 2011

BACKGROUND: Glioblastomas, the most common primary brain tumors in adults, still continue to have a predominantly fatal outcome. We previously cloned NPAS3 (neuronal PAS 3), a gene which is among the largest genes in the human genome and encodes a transcription factor. We recently discovered NPAS3 drives the progression of malignant astrocytomas as a tumor suppressor, by modulating the cell cycle, proliferation, apoptosis, and cell migration/invasion, and has a further influence on angiogenesis. In human glioblastoma surgical specimens, up to 75% demonstrate aberrant NPAS3 protein expression. In this study, we evaluated the expression of NPAS3 in the overall survival of patients diagnosed with glioblastomas. METHODS AND RESULTS: We examined a panel of glioblastomas from 77 postoperative patients who had total resection of the tumor. Postoperative patients were treated by standard adjuvant radiation therapy (60 Gy, 6 to 7 weeks) combined with chemotherapy, with a study follow-up not exceeding 30 months. Among the glioblastomas, 28 had absent, 18 had elevated, and 31 had normal NPAS3 expression. There were 54 males and 23 females in this study, with a median age of 59 years. In this study, patients with glioblastomas who had absent NPAS3 expression were identified as having the poorest overall survival compared with patients with glioblastomas who had normal or elevated NPAS3 expression (log-rank P value <0.001). Such a trend is still maintained even when patients are stratified among different age groups (<60 and >60 years). However, no significant difference in overall survival among patients with glioblastomas who had either normal or elevated NPAS3 expression was noted (log-rank P value >0.05). Likewise, no significant difference in gender versus overall survival noted. CONCLUSION: Our findings are of clinical importance by demonstrating that NPAS3 is an informative negative prognostic survival marker in patients with glioblastomas.

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-OMICS AND PROGNOSTIC MARKERS

OM- 0 2 5 7 9 12 20 23 27 28 29 52 56 . PRELIMINARY USE OF DIFFERENTIAL SCANNING CALORIMETRY OF CEREBROSPINAL FLUID 0 2 5 7 9 12 20 23 27 28 29 52 56 BRAIN TUMOR CELLS LINES 0 2 5 7 9 12 20 23 27 28 29 52 56 PATIENT TUMOR SAMPLES: CORRELATION WITH TUMOR HISTOLOGY 0 2 5 7 9 12 20 23 27 28 29 52 56 PATIENT OUTCOME 0 2 5 7 9 12 20 23 27 28 29 52 56 0 OM-04. MULTIDIMENSIONAL INTEGRATED MOLECULAR PROFILING OF GRADE II & III DIFFUSE ASTROCYTOMAS REVEAL DISTINCT SUBCLASSES CORRELATED WITH CLINICAL OUTCOME Daniel Gorovets, Edward R. Kastenhuber, Elena Pentsova, Lakshmi Nayak, and Jason T. Huse; Memorial Sloan-Kettering Cancer Center , New York, NY 1 CHAUQ Hoˆ pital de l'Enfant-Je ́sus , Quebec, QC , Canada 2 Randy L. Jensen; Huntsman Cancer Institute, University of Utah , Salt Lake City, UT 3 University Health Network , Toronto, ON , Canada 4 Centre de recherche de l'Hoˆ tel-Dieu de Que ́bec , Quebec, QC , Canada 5 OM-01. NPAS3 IS A NEGATIVE PROGNOSTIC SURVIVAL MARKER IN GLIOBLASTOMAS Frederico Moriera 6 Laval University , Quebec, QC , Canada 7 OM-07. THE MGMT-DEPENDENT “METHYLOME” IN GLIOBLASTOMA AND ANAPLASTIC GLIOMA Christiane Grimm 8 University Hospital Z u ̈rich , Z u ̈rich , Switzerland 9 OM-06. MIR-181D: A PREDICTIVE GLIOBLASTOMA BIOMARKER THAT DOWNREGULATES MGMT EXPRESSION Wei Zhang 10 Heidelberg University Hospital , Heidelberg , Germany 11 German Cancer Research Center , Heidelberg , Germany 12 OM-05. A CPG ISLAND HYPERMETHYLATED PHENOTYPE (CIMP) IN ANAPLASTIC OLIGODENDROGLIAL BRAIN TUMORS IS A BETTER PREDICTOR OF SURVIVAL THAN MGMT METHYLATION. A REPORT OF EORTC STUDY 26951 Martin J. van den Bent 13 Dept of Neurosurgery, Harbin Medical University , Harbin , China 14 Dept of Neurosurgery , Jiangsu Provincial People's Hosp, Nanjing , China 15 Laboratory of Neuro-Oncology, Tianjin Hospital , China 16 Division of Neurosurgery, University of California , San Diego, CA 17 Dana Farber Cancer Institute , Boston, MA 18 Peking University School of Oncology , Beijing , China 19 Beijing Genomics Institute , Shenzhen , China 20 OM-13. ELUCIDATION OF RESISTANCE TO TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME Lotte Hiddingh 21 RUNMC , Nijmegen , Netherlands 22 VU University Medical Center , Amsterdam , Netherlands 23 OM-09. CANCER PATHWAY DISCOVERY IN A MOUSE MODEL OF MEDULLOBLASTOMA Melanie Hayden Gephart 24 North Shore Private Hospital, Northern Cancer Institute , Sydney , Australia 25 Kolling Institute of Medical Research, University of Sydney , Sydney , Australia 26 Prince of Wales Clinical School, University of New South Wales , Sydney , Australia 27 OM-17. ABERRANT EXPRESSION OF LOW-MOLECULAR-WEIGHT PROTEINS ASSOCIATED WITH RESPONSE TO CONVENTIONAL CONCURRENT CHEMORADIOTHERAPY TREATMENT Hatice Sevim 28 OM-29. THE PROGNOSTIC VALUE OF IDH1 MUTATIONS IN GLIOMAS Rikke H. Dahlrot 29 OM-27. THE EFFECT OF TUMOR SUBTYPE ON SURVIVAL AND THE GRADED PROGNOSTIC ASSESSMENT (GPA) FOR PATIENTS WITH BREAST CANCER AND BRAIN METASTASES Paul W. Sperduto 30 Dana Farber Cancer Institute, Dept of Medical Oncology , Boston, MA 31 Yale University, School of Medicine, Dept of Radiation Oncology , New Haven, CT 32 Dartmouth College , Hanover, NH 33 University of Alabama , Birmingham , Dept of Radiation Oncology , Birmingham, AL 34 Yale University School of Medicine, Dept of Neurosurgery , New Haven, CT 35 Duke Medical Center, Dept of Radiation Oncology , Durham, NC 36 University of Colorado, School of Medicine, Dept of Radiation Oncology , Aurora, CO 37 Mayo Clinic , Radiation Oncology, Rochester, MN 38 Massachusetts General Hospital, Harvard Medical School, Dept. of Radiation Oncology , Boston, MA 39 McGill University Health Center, Dept. of Radiation Oncology , Montreal, QC , Canada 40 Northwestern University, Dept of Radiation Oncology , Chicago, IL 41 Department of Clinical Pathology, Odense University Hospital , Odense , Denmark 42 Department of Oncology, Odense University Hospital , Odense , Denmark 43 University of Wisconsin, Dept. of Human Oncology , Madison, WI 44 University of California San Francisco, Dept. of Radiation Oncology , San Francisco, MN 45 University of Minnesota, School of Public Health , Biostatistics, Minneapolis, MN 46 University of Minnesota, Masonic Cancer Center , Minneapolis, MN 47 Cleveland Clinic, Dept of Neurosurgery , Cleveland, OH 48 Cleveland Clinic, Dept. of Radiation Oncology , Cleveland, OH 49 Centre Hospitalier Universitaire Vaudois , Lausanne , Switzerland 50 The Radiation Therapy Oncology Group , Philadelphia, PA 51 The University of Texas MD Anderson Cancer Center , Houston, TX 52 OM-30. A COMBINED MOLECULAR CLINICAL PREDICTOR OF SURVIVAL VALIDATED WITH THE RTOG-0525 COHORT Erik P. Sulman 53 Northwestern University , Chicago, IL 54 CHUV , Lausanne , Switzerland 55 Radiation Therapy Oncology Group , Philadelphia, PA 56 OM-35. CLINICAL UTILITY OF G-CIMP AND IDH1 STATUS AS DUAL PROGNOSTIC MARKERS IN GLIOBLASTOMA Kenneth D. Aldape 57 Northwestern University Medical School , Evanston, IL Published by Oxf (...truncated)


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Frederico Moriera, Kelvin So, Peter Gould, Deepak Kamnasaran, Randy L. Jensen, Ibrahim Hussain, David H. Gutmann, Daniel Gorovets, Edward R. Kastenhuber, Elena Pentsova, Lakshmi Nayak, Jason T. Huse, Martin J. van den Bent, Lonneke A. Gravendeel, Thierry Gorlia, Johan M. Kros, Pieter Wesseling, Johannes Teepen, Ahmed Idbaih, Marc Sanson, Peter A Sillesvis Smitt, Pim J. French, Wei Zhang, Jing Zhang, Katherine Hoadley, Bob Carter, Shouwei Li, Chunsheng Kang, Yongping You, Chuanlu Jiang, Sonya Song, Tao Jiang, Clark Chen, Christiane Grimm, Markus Weiler, Rainer Claus, Dieter Weichenhan, Christian Hartmann, Christoph Plass, Michael Weller, Wolfgang Wick, Robert B. Jenkins, Hugues Sicotte, Yuanyuan Xiao, Brooke L. Fridley, Paul A. Decker, Matthew L. Kosel, Thomas M. Kollmeyer, Stephanie R. Fink, Amanda L. Rynearson, Terri Rice, Lucie S. McCoy, Ivan Smirnov, Tarik Tehan, Helen M. Hansen, Joseph S. Patoka, Michael D. Prados, Susan M. Chang, Mitchel S. Berger, Daniel H. Lachance, John K. Wiencke, Joseph L. Wiemels, Margaret R. Wrensch, Melanie Hayden Gephart, Eunice Lee, Sofia Kyriazopoulou-Panagiotopoulou, Ljiljana Milenkovic, Xu Xun, Yong Hou, Wu Kui, Michael Edwards, Serafim Batzoglou, Wang Jun, Matthew Scott, Jennifer E. Hobbs, Jeremiah Tipton, Tom Zhou, Neil L. Kelleher, James P. Chandler, Johannes Schwarzenberg, Johannes Czernin, Timothy Cloughesy, Benjamin Ellingson, Cheri Geist, Mike Phelps, Wei Chen, Mitsutoshi Nakada, Yutaka Hayashi, Wataru Obuchi, Sumio Ohtsuki, Takuya Watanabe, Chiemi Ikeda, Kouichi Misaki, Daisuke Kita, Yasuhiko Hayashi, Naoyuki Uchiyama, Tetsuya Terasaki, Jun-ichiro Hamada, Lotte Hiddingh, Bastiaan Tops, Esther Hulleman, Gert-Jan L. Kaspers, W. Peter Vandertop, Pieter Wesseling, David P. Noske, Tom Wurdinger, Judith W. Jeuken, Alfred Pokmeng See, Taeyoung Hwang, Dongjin Shin, Joo Heon Shin, Yuan Gao, Michael Lim, Markus Hutterer, Medinger Michael, Untergasser Gerold, Steinlechner Karin, Gstrein Ingrid, Deisenhammer Florian, Muigg Armin, Trinka Eugen, Gunsilius Eberhard, Stockhammer Günther, Robert W. Cook, Kristen Oelschlager, Hatice Sevim, Liping Chung, Helen T. Wheeler, Robert C. Baxter, Kerrie L. McDonald, Abhishek Chaturbedi, Liping Yu, Yi-Hong Zhou, Abhishek Chaturbedi, Anthony Wong, Remi Fatuyi, Mark E. Linskey, Yi-Hong Zhou, Iris Lavon, Tal Shahar, Daniel Zrihan, Avital Granit, Zvi Ram, Tali Siegal, Daniel J. Brat, Lee A. Cooper, David A. Gutman, Candace S. Chisolm, Christina Appin, Jun Kong, Tahsin Kurc, Erwin G. Van Meir, Joel H. Saltz, Carlos S. Moreno, Hazem J. Abuhusain, Kerrie L. McDonald, Anthony S. Don, Raman P. Nagarajan, Brett E. Johnson, Adam B. Olshen, Ivan Smirnov, Mingchao Xie, Jiexun Wang, Vasavi Sundaram, Pamela Paris, Ting Wang, Joseph F. Costello, Angelique E. Sijben, Sandra H. Boots-Sprenger, Jeroen Boogaarts, Jos Rijntjes, Johanna M. Geitenbeek, Job van der Palen, Hans J. Bernsen, Pieter Wesseling, Judith W. Jeuken, Oliver Schnell, S.A. Adam, Sabina Eigenbrod, Hans A. Kretzschmar, Jörg-Christian Tonn, Ulrich Schüller, Johannes Schwarzenberg, Timothy Cloughesy, Johannes Czernin, Cheri Geist, Mike Phelps, Wei Chen, Paul W. Sperduto, Norbert Kased, David Roberge, Zhiyuan Xu, Ryan Shanley, Xianghua Luo, Penny K. Sneed, Samuel T. Chao, Robert J. Weil, John Suh, Amit Bhatt, Ashley W. Jensen, Paul D. Brown, Helen A. Shih, John Kirkpatrick, Laurie E. Gaspar, John B. Fiveash, Veronica Chiang, Jonathan P. Knisely, Christina M. Sperduto, Nancy Lin, Minesh P. Mehta, Madan M. Kwatra, Tara M. Porter, Kristine E. Brown, James E. Herndon, Darell D. Bigner, Rikke H. Dahlrot, Bjarne W. Kristensen, Steinbjørn Hansen, Erik P. Sulman, Daniel P. Cahill, Meihau Wang, Minhee Won, Monika E. Hegi, Minesh P. Mehta, Ken D. Aldape, Mark R. Gilbert, Emad Seyed Sadr, Alain Tessier, Mohamed Seyed Sadr, Jad Alshami, Carmen Sabau, Rolando Del Maestro, Maxwell L. Neal, Russell Rockne, Andrew D. Trister, Kristin R. Swanson, Sanaz Maleki, Michael Back, Michael Buckland, David Brazier, Kerrie McDonald, Raymond Cook, Nicole Parker, Helen Wheeler, Llewellyn Jalbert, Adam Elkhaled, Joanna J. Phillips, Hikari A. Yoshihara, Rupa Parvataneni, Radhika Srinivasan, Gabriela Bourne, Susan M. Chang, Soonmee Cha, Sarah J. Nelson, Kenneth D. Aldape, Mark Gilbert, Daniel Cahill, Meihua Wang, Minhee Won, Monika Hegi, Howard Colman, Minesh Mehta, Erik Sulman, Adam Elkhaled, Llewellyn Jalbert, Alexandra Constantin, Joanna Phillips, Hikari Yoshihara, Radhika Srinivasan, Gabriela Bourne, Susan M. Chang, Soonmee Cha, Sarah Nelson, Shelly Gunn, Xavier T. Reveles, Budi Tirtorahardjo, Michelle N. Strecker, Lisa Fichtel. -OMICS AND PROGNOSTIC MARKERS, Neuro-Oncology, 2011, pp. iii76-iii84, 13/suppl 3, DOI: 10.1093/neuonc/nor167