Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Current criteria for the diagnosis of malignant GISTs do not always reliably predict patient outcomes. In order to search for genetic markers with prognostic potential, chromosomal imbalance aberrations (CIAs) were analyzed in 28 subjects with GIST using comparative genomic hybridization and correlated with clinicopathological features. Except for a small rectal tumor, CIAs were identified in all GISTs, including 14 from the stomach, 11 from the small intestine, 1 from the esophagus, and 1 from the rectum. Losses were more common than gains. The median number of CIAs in high-risk GISTs was significantly higher than that in low-risk GISTs (5.60±2.59 vs. 3.38±2.55; p<0.05), especially for losses (4.60±1.84 vs. 2.63±2.13; p<0.01). Loss of 14q was the most common CIA in both low-risk and high-risk GISTs, and can be regarded as an early event of GIST development. Losses of 1p and 15q were also very common, often coexisting, and were slightly more frequent in high-risk GISTs than in low-risk GISTs. Other recurrent CIAs, including losses of 10q, 13q, 15q, 18q, and 22q and gains of 5p, 12q, 17q, and 20q were relatively less common in this series. Among these CIAs, losses of 13q, 10q (with minimal overlapping on q11–q22), and 22q were most likely the chromosomal loci potentially harboring the tumor suppressor gene(s) which may be related to early recurrence and/or metastasis during malignant transformation of GISTs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ballarini C, Intra M, Ceretti AP, Prestipino F, Bianchi FM, Sparacio F, Berti E, Perrone S, Silva F. Gastrointestinal stromal tumors: a ‘benign’ tumor with hepatic metastasis after 11 years. Tumori 84:78–81;1998.
Breiner JA, Meis-Kindblom J, Kindblom LG, McComb E, Liu J, Nelson M, Bridge JA. Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors). Cancer Genet Cytogenet 120:111–116;2000.
Corless CL, McGreevey L, Haley A, Town A, Heinrich MC. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 160:1567–1572;2002.
Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol 33:466–477;2002.
Derré J, Lagacé R, Terrier P, Sastre X, Aurias A. Consistent DNA losses on the short arm of chromosome 1 in a series of malignant gastrointestinal stromal tumors. Cancer Genet Cytogenet 127:30–33;2001.
El-Rifai W, Sarlomo-Rikala M, Andersson LC, Knuutila S, Miettinen M. DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. Cancer Res 60:3899–3903;2000.
El-Rifai W, Sarlomo-Rikala M, Andersson LC, Miettinen M, Knuutila S. High-resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci. Genes Chromosomes Cancer 27:387–391;2000.
Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: Analysis of results in 140 surgically resected patients. Gastric Cancer 6:39–48;2003.
Gunawan B, Bergmann F, Hoer J, Langer C, Schumpelick V, Becker H, Fuzesi L. Biological and clinical significance of cytogenetic abnormalities in low-risk and high-risk gastrointestinal stromal tumors. Hum Pathol 33:316–321;2002.
Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S. Gastrointestinal stromal tumor: consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol 33:669–676;2002.
Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 33:484–95;2002.
Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821;1992.
Kim NG, Kim JJ, Ahn JY, Seong CM, Noh SH, Kim CB, Min JS, Kim H. Putative chromosomal deletions on 9P, 9Q and 22Q occur preferentially in malignant gastrointestinal stromal tumors. Int J Cancer 85:633–638;2000.
Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259–1269;1998.
Kirchhoff M, Gerdes T, Rose H, Maahr J, Ottesen AM, Lundsteen C. Detection of chromosomal gains and losses in comparative genomic hybridization analysis based on standard reference intervals. Cytometry 31:163–173;1998.
Knuutila S, Aalto Y, Autio K, Bjorkqvist AM, El-Rifai W, Hemmer S, Huhta T, Kettunen E, Kiuru-Kuhlefelt S, Larramendy ML, Lushnikova T, Monni O, Pere H, Tapper J, Tarkkanen M, Varis A, Wasenius VM, Wolf M, Zhu Y. DNA copy number losses in human neoplasms. Am J Pathol 155:683–694;1999.
Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M. Mutations in exon 11 of c-kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 154:53–60;1999.
Miettinen M, El-Rifai W, H L Sobin L, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: A review. Hum Pathol 33:478–483;2002.
Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. Am J Surg Pathol 25:1121–1133;2001.
Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Esophageal stromal tumors: A clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol 24:211–222;2000.
Morey AL, Wanigesekera GD, Hawkins NJ, Ward RL. C-kit mutations in gastrointestinal stromal tumours. Pathology 34:315–319;2002.
Nishida T, Nakamura J, Taniguchi M, Hirota S, Ito T, Kitamura Y, Matsuda H. Clinicopathological features of gastric stromal tumors. Exp Clin Cancer Res 19:417–425;2000.
Rudolph P, Chiaravalli AM, Pauser U, Oschlies I, Hillemanns M, Gobbo M, Marichal M, Eusebi V, Hofler H, Capella C, Kloppel G. Gastrointestinal mesenchymal tumors — immunophenotypic classification and survival analysis. Virchows Arch 441:238–248;2002.
Taniguchi M, Nishida T, Hirota S, Isozaki K, Ito T, Nomura T, Matsuda H, Kitamura Y. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 59:4297–4300;1999.
Tornoczky T, Kover E, Pajor L. Frequent occurrence of low grade cases among metastatic gastrointestinal stromal tumours. J Clin Pathol 56:363–367;2003.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, Y., Tzeng, CC., Liou, CP. et al. Biological significance of chromosomal imbalance aberrations in gastrointestinal stromal tumors. J Biomed Sci 11, 65–71 (2004). https://doi.org/10.1007/BF02256550
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02256550