Scram1 is a modifier of spinal cord resistance for astrocytoma on mouse Chr 5
Tumor location can profoundly affect morbidity and patient prognosis, even for the same tumor type. Very little is known about whether tumor location is determined stochastically or whether genetic risk factors can affect where tumors arise within an organ system. We have taken advantage of the Nf1−/+;Trp53−/+cis mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether astrocytomas are found in the spinal cord. We identify a locus on distal Chr 5, termed Scram1 for spinal cord resistance to astrocytoma modifier 1, with a LOD score of 5.0 and a genome-wide significance of P < 0.004. Mice heterozygous for C57BL/6J×129S4/SvJae at this locus show less astrocytoma in the spinal cord compared to 129S4/SvJae homozygous mice, although we have shown previously that 129S4/SvJae mice are more resistant to astrocytoma than C57BL/6J. Furthermore, the astrocytomas that are found in the spinal cord of Scram1 heterozygous mice arise in older mice. Because spinal cord astrocytomas are very rare and difficult to treat, a better understanding of the genetic factors that govern astrocytoma in the spine may lead to new targets of therapy or prevention.
KeywordsSpinal Cord Astrocytoma Spinal Cord Tumor Spinal Cord Section Backcross Mouse
We thank M. Anvers, R. Tuskan, K. Smith, K. Fox, and E. Truffer for technical assistance and D. Louis and G. Jallo for helpful discussions. JCAVS is a predoctoral student in the Graduate Partnership Program of the NIH and the Institute for Biomedical Sciences at George Washington University. This work is from a dissertation to be prepared in partial fulfillment of the requirements for the PhD degree. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsements by the US Government. This work was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (ZIA BC 010539 to KMR), federal funds from the National Cancer Institute to SAIC Frederick (contract N01-CO-12400), federal contract from the National Institutes of Health to The Johns Hopkins University (contract HHSN268200782096C), and extramural funding from the National Institutes of Health (R01 GM074244 to KWB).
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