| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communication |
From the Departments of Pathology*and Medicine,Division of Hematology/Oncology, Oregon Health and Science University, Portland; and the Portland Veterans Affairs Medical Center, Portland, Oregon
Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall that express the receptor tyrosine kinase KIT. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of studies of GISTs, although the reported frequency of these mutations has varied over a wide range (20 to 92%). Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 11 of KIT are a negative prognostic factor. To maximize sensitivity for KIT mutations we have adapted denaturing high-pressure liquid chromatography as a method for screening polymerase chain reaction amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was used to assess the frequency of KIT mutations in 13 morphologically benign, incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy for unrelated disease. Representing the smallest pathologically recognizable GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence-confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9, 11, and 17; one of these was also analyzed for exon 13 and was wild type in this exon as well. The mutations found in the incidental GISTs were identical to those that have been documented in larger GISTs. In addition, the overall frequency of mutations in the incidental tumors (85%) did not differ significantly from that we previously reported in a series of 72 advanced/metastatic GISTs (86%), strongly supporting the view that activating mutations in KIT are acquired very early in the development of most GISTs. The findings suggest that KIT mutations per se are of little prognostic importance in GISTs.
This article has been cited by other articles:
 |
|
 |
|
  F. S. Hodi, P. Friedlander, C. L. Corless, M. C. Heinrich, S. Mac Rae, A. Kruse, J. Jagannathan, A. D. Van den Abbeele, E. F. Velazquez, G. D. Demetri, et al. Major Response to Imatinib Mesylate in KIT-Mutated Melanoma J. Clin. Oncol., April 20, 2008; 26(12): 2046 - 2051. [Full Text] [PDF]
|
|
|
|
 |
|
 A L Gomes, A Gouveia, A F Capelinha, D de la Cruz, P Silva, R M Reis, A Pimenta, and J M Lopes Molecular alterations of KIT and PDGFRA in GISTs: evaluation of a Portuguese series J. Clin. Pathol., February 1, 2008; 61(2): 203 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Cassier, A. Dufresne, and J.-Y. Blay Controversies in the Adjuvant Treatment of Gastrointestinal Stromal Tumors (GIST) with Imatinib ASCO Educational Book, January 1, 2008; 2008(1): 524 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rutkowski, Z. I. Nowecki, W. Michej, M. Debiec-Rychter, A. Wozniak, J. Limon, J. Siedlecki, U. Grzesiakowska, M. Kakol, C. Osuch, et al. Risk Criteria and Prognostic Factors for Predicting Recurrences After Resection of Primary Gastrointestinal Stromal Tumor Ann. Surg. Oncol., July 1, 2007; 14(7): 2018 - 2027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zamo, A. Bertolaso, I. Franceschetti, G. Weirich, P. Capelli, S. Pecori, M. Chilosi, H. Hoefler, F. Menestrina, and A. Scarpa Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors: Diagnostic Applications and Report of a New KIT Mutation J. Mol. Diagn., April 1, 2007; 9(2): 151 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R Stewart, C. L Corless, B. P Rubin, M. C Heinrich, L. M Messiaen, L. J Kessler, P. J Zhang, and D. G Brooks Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1 J. Med. Genet., January 1, 2007; 44(1): e61 - e61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Corless, P. Harrell, M. Lacouture, T. Bainbridge, C. Le, K. Gatter, C. White Jr, S. Granter, and M. C. Heinrich Allele-Specific Polymerase Chain Reaction for the Imatinib-Resistant KIT D816V and D816F Mutations in Mastocytosis and Acute Myelogenous Leukemia J. Mol. Diagn., November 1, 2006; 8(5): 604 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bauer, L. K. Yu, G. D. Demetri, and J. A. Fletcher Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res., September 15, 2006; 66(18): 9153 - 9161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Tornillo and L M Terracciano An update on molecular genetics of gastrointestinal stromal tumours. J. Clin. Pathol., June 1, 2006; 59(6): 557 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Martin, A. Poveda, A. Llombart-Bosch, R. Ramos, J. A. Lopez-Guerrero, J. G. del Muro, J. Maurel, S. Calabuig, A. Gutierrez, J. L. G. de Sande, et al. Deletions Affecting Codons 557-558 of the c-KIT Gene Indicate a Poor Prognosis in Patients With Completely Resected Gastrointestinal Stromal Tumors: A Study by the Spanish Group for Sarcoma Research (GEIS) J. Clin. Oncol., September 1, 2005; 23(25): 6190 - 6198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Corless, A. Schroeder, D. Griffith, A. Town, L. McGreevey, P. Harrell, S. Shiraga, T. Bainbridge, J. Morich, and M. C. Heinrich PDGFRA Mutations in Gastrointestinal Stromal Tumors: Frequency, Spectrum and In Vitro Sensitivity to Imatinib J. Clin. Oncol., August 10, 2005; 23(23): 5357 - 5364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Rubin, C. R. Antonescu, J. P. Scott-Browne, M. L. Comstock, Y. Gu, M. R. Tanas, C. B. Ware, and J. Woodell A Knock-In Mouse Model of Gastrointestinal Stromal Tumor Harboring Kit K641E Cancer Res., August 1, 2005; 65(15): 6631 - 6639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. P. Li, J. A. Fletcher, M. C. Heinrich, J. E. Garber, S. E. Sallan, C. Curiel-Lewandrowski, A. Duensing, M. van de Rijn, L. E. Schnipper, and G. D. Demetri Familial Gastrointestinal Stromal Tumor Syndrome: Phenotypic and Molecular Features in a Kindred J. Clin. Oncol., April 20, 2005; 23(12): 2735 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Blay, S. Bonvalot, P. Casali, H. Choi, M. Debiec-Richter, A. P. Dei Tos, J.-F. Emile, A. Gronchi, P. C. W. Hogendoorn, H. Joensuu, et al. Consensus meeting for the management of gastrointestinal stromal tumors * Report of the GIST Consensus Conference of 20-21 March 2004, under the auspices of ESMO Ann. Onc., April 1, 2005; 16(4): 566 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. De Giorgi and J. Verweij Imatinib and gastrointestinal stromal tumors: Where do we go from here? Mol. Cancer Ther., March 1, 2005; 4(3): 495 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sihto, M. Sarlomo-Rikala, O. Tynninen, M. Tanner, L. C. Andersson, K. Franssila, N. N. Nupponen, and H. Joensuu KIT and Platelet-Derived Growth Factor Receptor Alpha Tyrosine Kinase Gene Mutations and KIT Amplifications in Human Solid Tumors J. Clin. Oncol., January 1, 2005; 23(1): 49 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Corless, L. McGreevey, A. Town, A. Schroeder, T. Bainbridge, P. Harrell, J. A. Fletcher, and M. C. Heinrich KIT Gene Deletions at the Intron 10-Exon 11 Boundary in GI Stromal Tumors J. Mol. Diagn., November 1, 2004; 6(4): 366 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Demetri, R. L. Titton, D. P. Ryan, and C. D.M. Fletcher Case 32-2004 - A 68-Year-Old Man with a Large Retroperitoneal Mass N. Engl. J. Med., October 21, 2004; 351(17): 1779 - 1787. [Full Text] [PDF]
|
|
|
|
|
|
S Carvalho, A O e Silva, F Milanezi, S Ricardo, D Leitao, I Amendoeira, and F C Schmitt c-KIT and PDGFRA in breast phyllodes tumours: overexpression without mutations? J. Clin. Pathol., October 1, 2004; 57(10): 1075 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Corless, J. A. Fletcher, and M. C. Heinrich Biology of Gastrointestinal Stromal Tumors J. Clin. Oncol., September 15, 2004; 22(18): 3813 - 3825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. West, C. L. Corless, X. Chen, B. P. Rubin, S. Subramanian, K. Montgomery, S. Zhu, C. A. Ball, T. O. Nielsen, R. Patel, et al. The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status Am. J. Pathol., July 1, 2004; 165(1): 107 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Eisenberg and I. Judson Surgery and Imatinib in the Management of GIST: Emerging Approaches to Adjuvant and Neoadjuvant Therapy Ann. Surg. Oncol., May 1, 2004; 11(5): 465 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Kim, H. Lee, Y.-K. Kang, M. S. Choe, M.-H. Ryu, H. M. Chang, J. S. Kim, J. H. Yook, B. S. Kim, and J. S. Lee Prognostic Significance of c-kit Mutation in Localized Gastrointestinal Stromal Tumors Clin. Cancer Res., May 1, 2004; 10(9): 3076 - 3081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kemmer, C. L. Corless, J. A. Fletcher, L. McGreevey, A. Haley, D. Griffith, O. W. Cummings, C. Wait, A. Town, and M. C. Heinrich KIT Mutations Are Common in Testicular Seminomas Am. J. Pathol., January 1, 2004; 164(1): 305 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Heinrich, C. L. Corless, G. D. Demetri, C. D. Blanke, M. von Mehren, H. Joensuu, L. S. McGreevey, C.-J. Chen, A. D. Van den Abbeele, B. J. Druker, et al. Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor J. Clin. Oncol., December 1, 2003; 21(23): 4342 - 4349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cruz III, B. P. Rubin, D. Wilson, A. Town, A. Schroeder, A. Haley, T. Bainbridge, M. C. Heinrich, and C. L. Corless Absence of BRAF and NRAS Mutations in Uveal Melanoma Cancer Res., September 15, 2003; 63(18): 5761 - 5766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Antonescu, G. Sommer, L. Sarran, S. J. Tschernyavsky, E. Riedel, J. M. Woodruff, M. Robson, R. Maki, M. F. Brennan, M. Ladanyi, et al. Association of KIT Exon 9 Mutations with Nongastric Primary Site and Aggressive Behavior: KIT Mutation Analysis and Clinical Correlates of 120 Gastrointestinal Stromal Tumors Clin. Cancer Res., August 1, 2003; 9(9): 3329 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rosai GIST: An Update International Journal of Surgical Pathology, July 1, 2003; 11(3): 177 - 186. [PDF]
|
|
|
|
|
|
R. Schneider-Stock, C. Boltze, J. Lasota, M. Miettinen, B. Peters, M. Pross, A. Roessner, and T. Gunther High Prognostic Value of p16INK4 Alterations in Gastrointestinal Stromal Tumors J. Clin. Oncol., May 1, 2003; 21(9): 1688 - 1697. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
