| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology, Pathobiology and Genetics |
1 Departments of Neurological Surgery (Brain Tumor Research Center) and 2 Laboratory Medicine, and 3 San Francisco General Hospital General Clinical Research Center, University of California, School of Medicine, San Francisco, California; and Departments of 4 Pathology, 5 Neuro-Oncology, 6 Biostatistics, and 7 Brain Tumor Center, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Requests for reprints: Kenneth D. Aldape, Department of Pathology, University of Texas M.D. Anderson Cancer Center, Box 85, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-7935; Fax: 713-745-1105; E-mail: kaldape{at}mdanderson.org.
Glioblastoma, the most aggressive primary brain tumor in humans, exhibits a large degree of molecular heterogeneity. Understanding the molecular pathology of a tumor and its linkage to behavior is an important foundation for developing and evaluating approaches to clinical management. Here we integrate array-comparative genomic hybridization and array-based gene expression profiles to identify relationships between DNA copy number aberrations, gene expression alterations, and survival in 34 patients with glioblastoma. Unsupervised clustering on either profile resulted in similar groups of patients, and groups defined by either method were associated with survival. The high concordance between these separate molecular classifications suggested a strong association between alterations on the DNA and RNA levels. We therefore investigated relationships between DNA copy number and gene expression changes. Loss of chromosome 10, a predominant genetic change, was associated not only with changes in the expression of genes located on chromosome 10 but also with genome-wide differences in gene expression. We found that CHI3L1/YKL-40 was significantly associated with both chromosome 10 copy number loss and poorer survival. Immortalized human astrocytes stably transfected with CHI3L1/YKL-40 exhibited changes in gene expression similar to patterns observed in human tumors and conferred radioresistance and increased invasion in vitro. Taken together, the results indicate that integrating DNA and mRNA-based tumor profiles offers the potential for a clinically relevant classification more robust than either method alone and provides a basis for identifying genes important in glioma pathogenesis.
Key Words: glioblastoma • clinical outcome • molecular marker • CHI3L1/YKL-40
This article has been cited by other articles:
|
|
 |
|
  J. S. Johansen, T. Lottenburger, H. J. Nielsen, J. E. B. Jensen, M. N. Svendsen, G. Kollerup, and I. J. Christensen Diurnal, Weekly, and Long-Time Variation in Serum Concentrations of YKL-40 in Healthy Subjects Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2603 - 2608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Colman and K. Aldape Molecular Predictors in Glioblastoma: Toward Personalized Therapy Arch Neurol, July 1, 2008; 65(7): 877 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lee, S. W. Kong, and P. J. Park Integrative analysis reveals the direct and indirect interactions between DNA copy number aberrations and gene expression changes Bioinformatics, April 1, 2008; 24(7): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Mantripragada, G. Spurlock, L. Kluwe, N. Chuzhanova, R. E. Ferner, I. M. Frayling, J. P. Dumanski, A. Guha, V. Mautner, and M. Upadhyaya High-Resolution DNA Copy Number Profiling of Malignant Peripheral Nerve Sheath Tumors Using Targeted Microarray-Based Comparative Genomic Hybridization Clin. Cancer Res., February 15, 2008; 14(4): 1015 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sabatino, Y. Zhao, S. Voiculescu, A. Monaco, P. Robbins, L. Karai, B. J. Nickoloff, M. Maio, S. Selleri, F. M. Marincola, et al. Conservation of Genetic Alterations in Recurrent Melanoma Supports the Melanoma Stem Cell Hypothesis Cancer Res., January 1, 2008; 68(1): 122 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. B. Furnari, T. Fenton, R. M. Bachoo, A. Mukasa, J. M. Stommel, A. Stegh, W. C. Hahn, K. L. Ligon, D. N. Louis, C. Brennan, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment Genes & Dev., November 1, 2007; 21(21): 2683 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Kim, M. Shago, L. Kaustov, P. C. Boutros, J. W. Clendening, Y. Sheng, G. A. Trentin, D. Barsyte-Lovejoy, D. Y.L. Mao, R. Kay, et al. CUL7 Is a Novel Antiapoptotic Oncogene Cancer Res., October 15, 2007; 67(20): 9616 - 9622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. W.-L. Wong, J. W. Clendening, A. Martirosyan, P. C. Boutros, C. Bros, F. Khosravi, I. Jurisica, A. K. Stewart, P. L. Bergsagel, and L. Z. Penn Determinants of sensitivity to lovastatin-induced apoptosis in multiple myeloma Mol. Cancer Ther., June 1, 2007; 6(6): 1886 - 1897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Park Integrated Analysis of Array-CGH and Expression Data Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 209 - 212. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Faury, A. Nantel, S. E. Dunn, M.-C. Guiot, T. Haque, P. Hauser, M. Garami, L. Bognar, Z. Hanzely, P. P. Liberski, et al. Molecular Profiling Identifies Prognostic Subgroups of Pediatric Glioblastoma and Shows Increased YB-1 Expression in Tumors J. Clin. Oncol., April 1, 2007; 25(10): 1196 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Byers, D. Di Vizio, F. O'Connell, E. Tholouli, R. M. Levenson, K. Gossard, D. Twomey, Y. Yang, E. Benedettini, J. Rose, et al. Semiautomated Multiplexed Quantum Dot-Based in Situ Hybridization and Spectral Deconvolution J. Mol. Diagn., February 1, 2007; 9(1): 20 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Maher, C. Brennan, P. Y. Wen, L. Durso, K. L. Ligon, A. Richardson, D. Khatry, B. Feng, R. Sinha, D. N. Louis, et al. Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities Cancer Res., December 1, 2006; 66(23): 11502 - 11513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liu, P. J. Park, W. Lai, E. Maher, A. Chakravarti, L. Durso, X. Jiang, Y. Yu, A. Brosius, M. Thomas, et al. A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma Cancer Res., November 15, 2006; 66(22): 10815 - 10823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hormigo, B. Gu, S. Karimi, E. Riedel, K. S. Panageas, M. A. Edgar, M. K. Tanwar, J. S. Rao, M. Fleisher, L. M. DeAngelis, et al. YKL-40 and Matrix Metalloproteinase-9 as Potential Serum Biomarkers for Patients with High-Grade Gliomas. Clin. Cancer Res., October 1, 2006; 12(19): 5698 - 5704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. N. van Wieringen, J. A. M. Belien, S. J. Vosse, E. M. Achame, and B. Ylstra ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data Bioinformatics, August 1, 2006; 22(15): 1919 - 1920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Pelloski, E Lin, L. Zhang, W.K. A. Yung, H. Colman, J.-L. Liu, S. Y. Woo, A. B. Heimberger, D. Suki, M. Prados, et al. Prognostic Associations of Activated Mitogen-Activated Protein Kinase and Akt Pathways in Glioblastoma. Clin. Cancer Res., July 1, 2006; 12(13): 3935 - 3941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, S. Diskin, E. Rappaport, E. Attiyeh, Y. Mosse, D. Shue, E. Seiser, J. Jagannathan, S. Shusterman, M. Bansal, et al. Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res., June 15, 2006; 66(12): 6050 - 6062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wrensch, J. K. Wiencke, J. Wiemels, R. Miike, J. Patoka, M. Moghadassi, A. McMillan, K. T. Kelsey, K. Aldape, K. R. Lamborn, et al. Serum IgE, Tumor Epidermal Growth Factor Receptor Expression, and Inherited Polymorphisms Associated with Glioma Survival. Cancer Res., April 15, 2006; 66(8): 4531 - 4541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Schmidt, J. S. Johansen, P. Sjoegren, I. J. Christensen, B. S. Sorensen, K. Fode, J. Larsen, and H. von der Maase Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma J. Clin. Oncol., February 10, 2006; 24(5): 798 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Johansen, B. V. Jensen, A. Roslind, D. Nielsen, and P. A. Price Serum YKL-40, A New Prognostic Biomarker in Cancer Patients? Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 194 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wrensch, T. Rice, R. Miike, A. McMillan, K. R. Lamborn, K. Aldape, and M. D. Prados Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area Neuro-oncol, January 1, 2006; 8(1): 12 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. French, S. M.A. Swagemakers, J. H.A. Nagel, M. C.M. Kouwenhoven, E. Brouwer, P. van der Spek, T. M. Luider, J. M. Kros, M. J. van den Bent, and P. A. Sillevis Smitt Gene Expression Profiles Associated with Treatment Response in Oligodendrogliomas Cancer Res., December 15, 2005; 65(24): 11335 - 11344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Bergmann, J. S. Johansen, T. W. Klausen, A. K. Mylin, J. S. Kristensen, E. Kjeldsen, and H. E. Johnsen High Serum Concentration of YKL-40 Is Associated with Short Survival in Patients with Acute Myeloid Leukemia Clin. Cancer Res., December 15, 2005; 11(24): 8644 - 8652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Alonso, J. Fueyo, J. W. Shay, K. D. Aldape, H. Jiang, O.-H. Lee, D. G. Johnson, J. Xu, Y. Kondo, T. Kanzawa, et al. Expression of Transcription Factor E2F1 and Telomerase in Glioblastomas: Mechanistic Linkage and Prognostic Significance J Natl Cancer Inst, November 2, 2005; 97(21): 1589 - 1600. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
