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Discriminate gene lists derived from cDNA microarray profiles of limited samples permit distinguishing mesenchymal neoplasia ex vivo

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Abstract

Background

Mesenchymal neoplasia comprises a heterogeneous group of tumors with over 200 benign neoplasms and 100 sarcomas. Currently, tumors are classified using histologic and immunocytologic characteristics, with diagnostic error rates reported as high as 40% of cases. As a feasibility study, our goal was to generate a preliminary discriminatory gene list for selected mesenchymal tumors, including sarcomas. This technique may enable an eventual molecular classification schema based on expression profiles that can complement current clinical and pathologic diagnostic procedures in mesenchymal tumors.

Methods

cDNA microarray analyses were preformed on connective tissue tumors obtained at time of surgical resection or biopsy. Messenger RNA (mRNA) from four general tumor classes was competitively hybridized against a human dermal fibroblast cell line comparator and the resulting gene expression profiles processed by ANOVA and linear discriminate analysis.

Results

The tissue classification involved 18 patients with malignant peripheral nerve sheath tumors, giant cell containing tumors, benign spindle cell lesions, or Ewing’s family of tumors. Lymph nodes from two patients served comparative purposes. Twenty-five differentially regulated genes considered most variable among the five tissue classes were identified. The tissues were segregated into five classes by linear discriminate analysis.

Conclusions

Linear discriminate analysis of cDNA gene expression profiles partitioned mesenchymal tumor classes, even when constrained by limited sample sizes.

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Acknowledgments

This project was supported by the Terri Anna Perine Sarcoma Fund and a grant from the Orthopaedic Research and Education Foundation. We thank Philip Moos and the faculty and staff of the Orthopedic Bioengineering Research Lab, Department of Orthopedics, for reviewing the manuscript, Ariel Rogers for collation and preparation of the tables, Laurent Perreard (ARUP Laboratories) for the real time RT-PCR analysis, and Matt McIff for technical assistance

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Author notes

  1. Karen H. Albritton

    Present address: Adolescent Oncology Program, Department of Pediatrics, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Authors and Affiliations

  1. SARC™ Lab, Sarcoma Services, Department of Orthopedics, Huntsman Cancer Institute & Primary Children’s Medical Center, 2000 Circle of Hope, University of Utah, Salt Lake City, UT, 84112, USA

    David E. Joyner, Jeffrey Bastar & R. Lor Randall

  2. Division of Hematology/Oncology, Departments of Medicine & Pediatrics, Huntsman Cancer Institute and Primary Children’s Medical Center, University of Utah, Salt Lake City, Utah, USA

    Karen H. Albritton

  3. Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Mark L.Wade & Aniko Szabo

  4. Department of Pathology, University of Utah, Salt Lake City, Utah, USA

    Philip S. Bernard

  5. Department of Pathology, Primary Children’s Medical Center, University of Utah, Salt Lake City, Utah, USA

    Cheryl M. Coffin

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  1. David E. Joyner
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Correspondence to R. Lor Randall.

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Joyner, D.E., L.Wade, M., Szabo, A. et al. Discriminate gene lists derived from cDNA microarray profiles of limited samples permit distinguishing mesenchymal neoplasia ex vivo. J Cancer Res Clin Oncol 131, 137–146 (2005). https://doi.org/10.1007/s00432-004-0640-1

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  • DOI: https://doi.org/10.1007/s00432-004-0640-1

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