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 A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve.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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References
Bajenaru ML, Donahoe J, Corral T, Reilly KM, Brophy S, Pellicer A, Gutmann DH . 2001 Glia 33: 314–323
Bajenaru ML, Zhu Y, Hedrick NM, Donahoe J, Parada LF, Gutmann DH . 2002 Mol. Cell. Biol. 22: 5100–5113
Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN . 1998 J. Natl. Cancer Int. 90: 1473–1479
Chiu IM, Touhalisky K, Liu Y, Yates A, Frostholm A . 2000 Oncogene 19: 6229–6239
Cichowski K, Shih TS, Schmitt E, Santiago S, Reilly K, McLaughlin ME, Bronson RT, Jacks T . 1999 Science 286: 2162–2167
Dai C, Celestino JC, Okada Y, Louis DN, Fuller GN, Holland EC . 2001 Genes Dev. 15: 1913–1925
Di Rocci F, Carroll RS, Zhang J, Black PM . 1998 Neurosurgery 42: 341–346
Ding H, Roncari L, Shannon P, Wu X, Lau N, Karaskova J, Gutmann DH, Squire JA, Nagy A, Guha A . 2001 Cancer Res. 61: 3826–3836
Fortin D, Cairncross GJ, Hammond RR . 1999 Neurosurgery 45: 1279–1291 discussion 191
Garcea RL . 2001 Dis. Markers 17: 149–151
Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G . 2000 Genes Dev. 14: 1617–1630
Goldowitz D, Hamre K . 1998 Trends Neurosci. 21: 375–382
Goodrich LV, Milenkovic L, Higgins KM, Scott MP . 1997 Science 277: 1109–1113
Hatten ME, Heintz N . 1995 Annu. Rev. Neurosci. 18: 385–408
Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN . 2000 Nat. Genet. 25: 55–57
Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA . 1994 Nat. Genet. 7: 353–361
Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK . 2002 J. Neuropathol. Exp. Neurol. 61: 215–225 discussion 226–229
Marino S, Vooijs M, van der Gulden H, Jonkers J, Berns A . 2000 Genes Dev. 14: 994–1004
McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T . 1997 Genes Dev. 11: 1253–1265
McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T . 1998 Genes Dev. 12: 1121–1133
Nordlund ML, Rizvi TA, Brannan CI, Ratner N . 1995 J. Neuropathol. Exp. Neurol. 54: 588–600
Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, Sorensen N, Berthold F, Henk B, Schmandt N, Wolf HK, von Deimling A, Wainwright B, Chenevix-Trench G, Wiestler OD, Wicking C . 1997 Cancer Res. 57: 2085–2088
Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR . 2002 Nature 415: 436–442
Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, James CD . 1997 Cancer Res. 57: 842–845
Reifenberger J, Reifenberger G, Ichimura K, Schmidt EE, Wechsler W, Collins VP . 1996 Am. J. Pathol. 149: 29–35
Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T . 2000 Nat. Genet. 26: 109–113
Rizvi TA, Akunuru S, de Courten-Myers G, Switzer III RC, Nordlund ML, Ratner N . 1999 Brain Res. 816: 111–123
Robinson S, Cohen M, Prayson R, Ransohoff RM, Tabrizi N, Miller RH . 2001 Neurosurgery 48: 864–873 discussion 873–874
Saenz Robles MT, Symonds H, Chen J, Van Dyke T . 1994 Mol. Cell. Biol. 14: 2686–2698
Sidman RL, Rakic P . 1973 Brain Res. 62: 1–35
Smith JS, Wang XY, Qian J, Hosek SM, Scheithauer BW, Jenkins RB, James CD . 2000 J. Neuropathol. Exp. Neurol. 59: 495–503
Symonds H, Krall L, Remington L, Saenz-Robles M, Lowe S, Jacks T, Van Dyke T . 1994 Cell 78: 703–711
Uhrbom L, Hesselager G, Nister M, Westermark B . 1998 Cancer Res. 58: 5275–5279
Van Dyke TA, Finlay C, Miller D, Marks J, Lozano G, Levine AJ . 1987 J. Virol. 61: 2029–2032
Vogel KS, Klesse LJ, Velasco-Miguel S, Meyers K, Rushing EJ, Parada LF . 1999 Science 286: 2176–2179
Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A . 1997 Oncogene 14: 2005–2013
Wetmore C, Eberhart DE, Curran T . 2000 Cancer Res. 60: 2239–2246
Wetmore C, Eberhart DE, Curran T . 2001 Cancer Res. 61: 513–516
Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G . 1997 Cancer Res. 57: 2581–2585
Xiao A, Wu H, Pandolfi PP, Louis DN, Van Dyke T . 2002 Cancer Cell 1: 157–168
Xie J, Johnson RL, Zhang X, Bare JW, Waldman FM, Cogen PH, Menon AG, Warren RS, Chen LC, Scott MP, Epstein Jr EH . 1997 Cancer Res. 57: 2369–2372
Zhu Y, Romero MI, Ghosh P, Ye Z, Charnay P, Rushing EJ, Marth JD, Parada LF . 2001 Genes Dev. 15: 859–876
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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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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DOI: https://doi.org/10.1038/sj.onc.1205936