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  • Original Paper
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Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles

Oncogene volume 23, pages 7780–7790 (2004)Cite this article

Abstract

Most GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that might contribute to these biological differences, we carried out gene expression profiling of 26 GISTs with known KIT and PDGFRA mutational status. Expression differences were then evaluated further by RNA in situ hybridization, immunohistochemistry, and immunoblotting. Unsupervised hierarchical clustering grouped tumors with similar mutations together, but the distinction between the different groups was not absolute. Differentially expressed genes included ezrin, p70S6K, and PKCs, which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute to the distinctive clinicopathological features in GISTs with different mutation types. These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated.

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Acknowledgements

SS was supported by a fellowship from the Laboratory of Surgical Pathology, Department of Pathology, Stanford University Medical Center. This work was supported by NIH Grant CA85129.

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Author notes

  1. Subbaya Subramanian and Robert B West: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Stanford University Medical Center, Stanford, CA, USA

    Subbaya Subramanian, Robert B West, Shirley Zhu, Kelli Montgomery & Matt van de Rijn

  2. Department of Pathology, Oregon Health and Science University, OHSU Cancer Institute and Portland VA Medical Center, Portland, OR, USA

    Christopher L Corless

  3. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    Wenbin Ou & Jonathan A Fletcher

  4. Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA, USA

    Brian P Rubin

  5. Department of Surgery, The University of Hong Kong, Hong Kong

    Kent-Man Chu

  6. Department of Pathology, The University of Hong Kong, Hong Kong

    Suet Yi Leung & Siu Tsan Yuen

  7. Department of Biochemistry, Stanford University Medical Center, Stanford, CA, USA

    Tina Hernandez-Boussard

  8. Department of Pathology and Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, BC, Canada

    Torsten O Nielsen

  9. Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Rajiv M Patel & John R Goldblum

  10. Department of Medicine, Oregon Health and Science University, OHSU Cancer Institute and Portland VA Medical Center, Portland, OR, USA

    Michael C Heinrich

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  1. Subbaya Subramanian
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Correspondence to Matt van de Rijn.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Subramanian, S., West, R., Corless, C. et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene 23, 7780–7790 (2004). https://doi.org/10.1038/sj.onc.1208056

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