This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nigro, J. M. Articles by Aldape, K. Search for Related Content PubMed PubMed Citation Articles by Nigro, J. M. Articles by Aldape, K.

(American Journal of Pathology. 2001;158:1253-1262.)
© 2001 American Society for Investigative Pathology

Technical Advance

Detection of 1p and 19q Loss in Oligodendroglioma by Quantitative Microsatellite Analysis, a Real-Time Quantitative Polymerase Chain Reaction Assay

Janice M. Nigro^*, Michelle A. Takahashi^*, David G. Ginzinger, Mark Law, Sandra Passe, Robert B. Jenkins and Ken Aldape^*

From the Department of Pathology,^*
University of California, San Francisco, San Francisco, California; the Department of Laboratory Medicine,
University of California, San Francisco Cancer Center, San Francisco, California; and the Departments of Laboratory Medicine and Pathology,
Mayo Clinic, Rochester, Minnesota

The combined loss of chromosomes 1p and 19q has recently emerged as a genetic predictor of chemosensitivity in anaplastic oligodendrogliomas. Here, we describe a strategy that uses a novel method of real-time quantitative polymerase chain reaction, quantitative microsatellite analysis (QuMA), for the molecular analysis of 1p and 19q loss in oligodendrogliomas and oligoastrocytomas in archival routinely processed paraffin material. QuMA is performed on the ABI 7700 and based on amplifications of microsatellite loci that contain (CA)n repeats where the repeat itself is the target for hybridization by the fluorescently labeled probe. This single probe can therefore be used to determine copy number of microsatellite loci spread throughout the human genome. In genomic DNA prepared from paraffin-embedded brain tumor specimens, QuMA detected combined loss of 1p and 19q in 64% (21 of 32) of oligodendrogliomas and 67% (6 of 9) of oligoastrocytomas. We validate the use of QuMA as a reliable method to detect copy number by showing concordance between QuMA and fluorescence in situ hybridization at 37 of 45 chromosomal arms tested. These results indicate that QuMA is an accurate, high-throughput assay for the detection of copy number at multiple loci; as many as 31 loci of an individual tumor can be analyzed on a 96-well plate in a single 2-hour run. In addition, it has advantages over standard allelic imbalance/loss of heterozygosity assays in that all loci are potentially informative, paired normal tissue is not required, and gain can be distinguished from loss. QuMA may therefore be a powerful molecular tool to expedite the genotypic analysis of human gliomas in a clinical setting for diagnostic/prognostic purposes.

This article has been cited by other articles:

				X. SUN, J. HUANG, T. HOMMA, D. KITA, H. KLOCKER, G. SCHAFER, P. BOYLE, and H. OHGAKI Genetic Alterations in the PI3K Pathway in Prostate Cancer Anticancer Res, May 1, 2009; 29(5): 1739 - 1743. [Abstract] [Full Text] [PDF]

				J. Huang, J. Pang, T. Watanabe, H.-K. Ng, and H. Ohgaki Whole Genome Amplification for Array Comparative Genomic Hybridization Using DNA Extracted from Formalin-Fixed, Paraffin-Embedded Histological Sections J. Mol. Diagn., March 1, 2009; 11(2): 109 - 116. [Abstract] [Full Text] [PDF]

				L. P. Gondek, R. Tiu, C. L. O'Keefe, M. A. Sekeres, K. S. Theil, and J. P. Maciejewski Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML Blood, February 1, 2008; 111(3): 1534 - 1542. [Abstract] [Full Text] [PDF]

				K. Fukino, L. Shen, A. Patocs, G. L. Mutter, and C. Eng Genomic Instability Within Tumor Stroma and Clinicopathological Characteristics of Sporadic Primary Invasive Breast Carcinoma JAMA, May 16, 2007; 297(19): 2103 - 2111. [Abstract] [Full Text] [PDF]

				M. Nakamura, K. Shimada, E. Ishida, T. Higuchi, H. Nakase, T. Sakaki, and N. Konishi Molecular pathogenesis of pediatric astrocytic tumors Neuro Oncology, April 1, 2007; 9(2): 113 - 123. [Abstract] [Full Text] [PDF]

				Y. Kotliarov, M. E. Steed, N. Christopher, J. Walling, Q. Su, A. Center, J. Heiss, M. Rosenblum, T. Mikkelsen, J. C. Zenklusen, et al. High-resolution Global Genomic Survey of 178 Gliomas Reveals Novel Regions of Copy Number Alteration and Allelic Imbalances Cancer Res., October 1, 2006; 66(19): 9428 - 9436. [Abstract] [Full Text] [PDF]

				J. Jeuken, S. Cornelissen, S. Boots-Sprenger, S. Gijsen, and P. Wesseling Multiplex Ligation-Dependent Probe Amplification: A Diagnostic Tool for Simultaneous Identification of Different Genetic Markers in Glial Tumors J. Mol. Diagn., September 1, 2006; 8(4): 433 - 443. [Abstract] [Full Text] [PDF]

				M. A. Patil, I. Gutgemann, J. Zhang, C. Ho, S.-T. Cheung, D. Ginzinger, R. Li, K. J. Dykema, S. So, S.-T. Fan, et al. Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma Carcinogenesis, December 1, 2005; 26(12): 2050 - 2057. [Abstract] [Full Text] [PDF]

				A. Misra, M. Pellarin, J. Nigro, I. Smirnov, D. Moore, K. R. Lamborn, D. Pinkel, D. G. Albertson, and B. G. Feuerstein Array Comparative Genomic Hybridization Identifies Genetic Subgroups in Grade 4 Human Astrocytoma Clin. Cancer Res., April 15, 2005; 11(8): 2907 - 2918. [Abstract] [Full Text] [PDF]

				P. S. Dahlberg, B. A. Jacobson, G. Dahal, J. M. Fink, R. A. Kratzke, M. A. Maddaus, and L. J. Ferrin ERBB2 Amplifications in Esophageal Adenocarcinoma Ann. Thorac. Surg., November 1, 2004; 78(5): 1790 - 1800. [Abstract] [Full Text] [PDF]

				H. Ohgaki, P. Dessen, B. Jourde, S. Horstmann, T. Nishikawa, P.-L. Di Patre, C. Burkhard, D. Schuler, N. M. Probst-Hensch, P. C. Maiorka, et al. Genetic Pathways to Glioblastoma: A Population-Based Study Cancer Res., October 1, 2004; 64(19): 6892 - 6899. [Abstract] [Full Text] [PDF]

				S. Suzuki, K. Egami, K. Sasajima, M. Ghazizadeh, H. Shimizu, H. Watanabe, H. Hasegawa, S. Iida, T. Matsuda, Y. Okihama, et al. Comparative Study between DNA Copy Number Aberrations Determined by Quantitative Microsatellite Analysis and Clinical Outcome in Patients with Stomach Cancer Clin. Cancer Res., May 1, 2004; 10(9): 3013 - 3019. [Abstract] [Full Text] [PDF]

				A. Perry Pathology of low-grade gliomas: An update of emerging concepts Neuro Oncology, July 1, 2003; 5(3): 168 - 178. [Abstract] [PDF]

				L. Del Valle, S. Enam, C. Lara, C. Ortiz-Hidalgo, C. D. Katsetos, and K. Khalili Detection of JC Polyomavirus DNA Sequences and Cellular Localization of T-Antigen and Agnoprotein in Oligodendrogliomas Clin. Cancer Res., November 1, 2002; 8(11): 3332 - 3340. [Abstract] [Full Text] [PDF]

				K. Farrand, L. Jovanovic, B. Delahunt, B. McIver, I. D. Hay, N. L. Eberhardt, and S. K. G. Grebe Loss of Heterozygosity Studies Revisited: Prior Quantification of the Amplifiable DNA Content of Archival Samples Improves Efficiency and Reliability J. Mol. Diagn., August 1, 2002; 4(3): 150 - 158. [Abstract] [Full Text] [PDF]

				K. Ueki, R. Nishikawa, Y. Nakazato, T. Hirose, J. Hirato, N. Funada, T. Fujimaki, S. Hojo, O. Kubo, T. Ide, et al. Correlation of Histology and Molecular Genetic Analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 Astrocytic and Oligodendroglial Tumors Clin. Cancer Res., January 1, 2002; 8(1): 196 - 201. [Abstract] [Full Text] [PDF]