Integrative genomic characterization and a genomic staging system for gastrointestinal stromal tumors

Authors

  • Antti Ylipää MSc,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Signal Processing, Tampere University of Technology, Tampere, Finland
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  • Kelly K. Hunt MD,

    1. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Jilong Yang MD, PhD,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
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  • Alexander J. F. Lazar MD, PhD,

    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Keila E. Torres MD,

    1. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Dina C. Lev MD,

    1. Department of Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Matti Nykter PhD,

    1. Department of Signal Processing, Tampere University of Technology, Tampere, Finland
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  • Raphael E. Pollock MD, PhD,

    1. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Jonathan Trent MD, PhD,

    1. Department of Sarcoma Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    2. Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Wei Zhang PhD

    Corresponding author
    1. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Pathology, Unit 85, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030
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    • Fax: (713) 792-5549


Abstract

BACKGROUND:

Gastrointestinal stromal tumors (GISTs) historically were grouped with leiomyosarcomas (LMSs) based on their morphologic similarities; however, recently, GIST was established unequivocally as a distinct type of sarcoma based on its molecular features and response to imatinib treatment.

METHODS:

To gain further insight into the genomic differences between GISTs and LMSs, the authors mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated the results with gene expression profiles.

RESULTS:

Distinct patterns of CNAs were revealed between GISTs and LMSs. Losses in 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < .001); whereas losses in chromosomes 10 and 16 and gains in 1q, 14q, and 15q (P < .001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, the authors identified several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into 4 groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were expressed differently in the 4 groups, and the patients in each group had increasingly worse prognoses as the extent of genomic alterations increased.

CONCLUSIONS:

Based on the current findings, the authors proposed a new tumor-progression genetic staging system termed genomic instability stage to complement the current prognostic predictive system based on tumor size, mitotic index, and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation. Cancer 2011. © 2010 American Cancer Society.

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