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Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum

Oncogene volume 21, pages 7453–7463 (2002)Cite this article

Abstract

The Mouse Models of Cancer Consortium of the NCI sponsored a meeting of neuropathologists and veterinary pathologists in New York City in November of 2000. A rapidly growing number of genetically engineered mice (GEM) predisposed to tumors of the nervous system have led to a concomitant need for neuropathological evaluation and validation of these models. A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve. The GEM tumors were found to have many similarities and some distinct differences with respect to human disease. After review of the biology and pathology for all models presented, participants were split into groups reflective of clinical expertise in human pathology, tumor biology, neuroimaging, or treatment/intervention. Recommendations were made detailing an extensive and complete neuropathological characterization of animals. Importance was placed on including information on strains, tumor clonality, and examination for genetic mutation or altered gene expression characteristics of the corresponding human malignancy. Specific proposals were made to incorporate GEM models in emerging neuroradiological modalities. Recommendations were also made for preclinical validation of these models in cancer therapeutics, and for incorporation of surrogate markers of tumor burden to facilitate preclinical evaluation of new therapies.

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Acknowledgements

WA Weiss and M Israel were the meeting organizers. WA Weiss edited the manuscript. K Aldape organized the pathology workshop, prepared and distributed slide sets, and prepared figures for the manuscript. Charles Cobbs, Eric Holland, C David James, David N Louis, Cheryl Marks, Andrea I McClatchey, Tim Roberts, Terry Van Dyke and Cynthia Wetmore contributed equally to writing subsections of this manuscript and are listed alphabetically. Ing-Ming Chiu, Marco Giovannini, Abhijit Guha, Robert J Higgins, Silvia Marino, Ivan Radovanovic and Karlyne Reilly contributed pathology specimens and are listed alphabetically following those who contributed to writing this manuscript. This meeting was sponsored by the Mouse Models of Human Cancer Consortium of the NCI. We would like to thank Susan Seweryniak, Angela Sammarco and Tricia Wallich for assistance in organizing this meeting, Brian Slater for assistance in digitizing images, and David Gutmann for critical review of the manuscript. We acknowledge our additional pathology panel members for also reviewing the slide set: Roderick Bronson, Peter C Burger, Robert Cardiff, V Peter Collins, Charles Eberhardt, Gregory N Fuller, Margaret McLaughlin, Bernd Scheithauer, Patrick Shannon and James Woodruff. We are grateful to the following investigators for providing information and materials for the slide sets: Adriano Aguzzi, Anton Berns, Henry Friedman, Yancy Gillespie, Tyler Jacks, Matthew Scott, Xiao-Yang Wang and Bengt Westermark. We also acknowledge these additional investigators for organizing specific sessions: Peter Burger, Howard Fine, Greg Fuller, Yancy Gillespie, Bob Jenkins, Andras Nagy, Michael Prados, James Provenzale, Brian Ross, Ed Shaw, James Woodruff and Al Yung.

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Authors and Affiliations

  1. Department of Neurology, University of California, 521 Parnassus Avenue, San Francisco, 94143-0114, California, CA, USA

    William A Weiss

  2. Department of Pediatrics, University of California, 521 Parnassus Avenue, San Francisco, 94143-0114, California, CA, USA

    William A Weiss

  3. Department of Neurological Surgery, University of California, 521 Parnassus Avenue, San Francisco, 94143-0114, California, CA, USA

    William A Weiss

  4. Department of Pediatrics, Dartmouth-Hitchcock Medical Center, One Medical Drive, Lebanon, 03756, New Hampshire, NH, USA

    Mark Israel

  5. Department of Genetics, Dartmouth-Hitchcock Medical Center, One Medical Drive, Lebanon, 03756, New Hampshire, NH, USA

    Mark Israel

  6. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, One Medical Drive, Lebanon, 03756, New Hampshire, NH, USA

    Mark Israel

  7. Department of Surgery, Division of Neurosurgery, University of Alabama at Birmingham, 1813 6th Avenue South, MEB 520, Birmingham, 35294, Alabama, AL, USA

    Charles Cobbs

  8. Department of Laboratory Medicine and Pathology, Mayo Clinic, Hilton Building, Room 820-D, Rochester, 55905, Minnesota, MN, USA

    Eric Holland

  9. Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, 10021, NY, USA

    Eric Holland

  10. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, 10021, NY, USA

    Eric Holland

  11. Department of Cell Biology, Memorial Sloan Kettering Cancer Center, New York, 10021, NY, USA

    C David James

  12. Department of Pathology, Neurosurgical Service and Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, MA, USA

    David N Louis

  13. Division of Cancer Biology, National Cancer Institute, 6130 Executive Blvd., EPN5000, Bethesda, 20892, Maryland, MD, USA

    Cheryl Marks

  14. Department of Pathology, MGH Cancer Center, Harvard Medical School, Building 149, 13th Street, Charlestown, 02129, Massachusetts, MA, USA

    Andrea I McClatchey

  15. Department of Medical Imaging, University of Toronto, Fitzgerald Building, 150 College Street, Room 127, Toronto, M5S 3E2, Ontario, Canada

    Tim Roberts

  16. 12-044 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599, North Carolina, NC, USA

    Terry Van Dyke

  17. Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic and Cancer Center, 200 First St SW, Rochester, 55905, Minnesota, MN, USA

    Cynthia Wetmore

  18. Department of Internal Medicine, Ohio State University, 480 West 9th Avenue, Columbus, 43210, Ohio, OH, USA

    Ing-Ming Chiu

  19. INSERM U434, Fondation Jean Dausset – CEPH, 27 rue Juliette Dodu, Paris, 75010, France

    Marco Giovannini

  20. Department of Surgery (Neurosurgery), Hospital for Sick Children, University of Toronto, 3017 McMaster Bld, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada

    Abhijit Guha

  21. Department of Pathology, Microbiology & Immunology, 1052 Haring Hall, University of California, Davis, 95616, California, CA, USA

    Robert J Higgins

  22. Institute of Neuropathology, University Hospital, Schmelzbergstrasse 12, Zürich, CH-8091, Switzerland

    Silvia Marino

  23. Institute of Clinical Pathology, University Hospital, Schmelzbergstrasse 12, Zürich, CH-8091, Switzerland

    Ivan Radovanovic

  24. MIT/Center for Cancer Research, Building E17-518, 40 Ames Street, Cambridge, 02139, Massachusetts, MA, USA

    Karlyne Reilly

  25. Department of Pathology and Brain Tumor Center, UT-MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, 77030, Texas, TX, USA

    Ken Aldape

Authors
  1. William A Weiss
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  2. Mark Israel
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  3. Charles Cobbs
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  5. C David James
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  7. Cheryl Marks
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  8. Andrea I McClatchey
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  9. Tim Roberts
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  10. Terry Van Dyke
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  11. Cynthia Wetmore
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  12. Ing-Ming Chiu
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  13. Marco Giovannini
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  15. Robert J Higgins
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  16. Silvia Marino
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  17. Ivan Radovanovic
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  18. Karlyne Reilly
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  19. Ken Aldape
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Corresponding author

Correspondence to William A Weiss.

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Weiss, W., Israel, M., Cobbs, C. et al. Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum. Oncogene 21, 7453–7463 (2002). https://doi.org/10.1038/sj.onc.1205936

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