This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Meza-Zepeda, L. A. Articles by Myklebost, O. Search for Related Content PubMed PubMed Citation Articles by Meza-Zepeda, L. A. Articles by Myklebost, O.

Array Comparative Genomic Hybridization Reveals Distinct DNA Copy Number Differences between Gastrointestinal Stromal Tumors and Leiomyosarcomas

Departments of ¹ Tumor Biology and ² Pathology, Rikshospitalet-Radiumhospitalet Medical Center; and ³ Department of Molecular Biosciences, and ⁴ Faculty Division, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway

Requests for reprints: Leonardo A. Meza-Zepeda, Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, N-0310 Oslo, Norway. Phone: 47-2293-5590; Fax: 47-2252-2421; E-mail: leonardm{at}radium.uio.no.

Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas. (Cancer Res 2006;66(18):8984-93)

This article has been cited by other articles:

				C. Tarn, L. Rink, E. Merkel, D. Flieder, H. Pathak, D. Koumbi, J. R. Testa, B. Eisenberg, M. von Mehren, and A. K. Godwin Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors PNAS, June 17, 2008; 105(24): 8387 - 8392. [Abstract] [Full Text] [PDF]

				N. D. Price, J. Trent, A. K. El-Naggar, D. Cogdell, E. Taylor, K. K. Hunt, R. E. Pollock, L. Hood, I. Shmulevich, and W. Zhang Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas PNAS, February 27, 2007; 104(9): 3414 - 3419. [Abstract] [Full Text] [PDF]