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

Antti Ylipää, Kelly K. Hunt, Jilong Yang, Alexander J.F. Lazar, Keila E. Torres, Dina C. Lev, Matti Nykter, Raphael E. Pollock, Jonathan Trent, Wei Zhang

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)380-389
Number of pages10
JournalCancer
Volume117
Issue number2
DOIs
StatePublished - Jan 15 2011

    Fingerprint

Keywords

  • array comparative genomic hybridization
  • copy number aberrations
  • gastrointestinal stromal tumors
  • imatinib
  • leiomyosarcoma
  • survival
  • v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ylipää, A., Hunt, K. K., Yang, J., Lazar, A. J. F., Torres, K. E., Lev, D. C., Nykter, M., Pollock, R. E., Trent, J., & Zhang, W. (2011). Integrative genomic characterization and a genomic staging system for gastrointestinal stromal tumors. Cancer, 117(2), 380-389. https://doi.org/10.1002/cncr.25594