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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-10-3091. This Article Full Text (PDF) All Versions of this Article: 2002-10-3091v1 101/7/2797    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Karlsson, A. Articles by Felsher, D. Search for Related Content PubMed PubMed Citation Articles by Karlsson, A. Articles by Felsher, D. Social Bookmarking                   What's this? Submitted October 11, 2002 Accepted November 18, 2002 Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations Asa Karlsson, Sylvie Giuriato, Flora Tang, Jingly Fung-Weier, Goran Levan, and Dean Felsher* Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA, USA; Cellular and Molecular Biology, Goteborg University, Goteborg, CA, USA Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA, USA Reproductive Genetics Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, UCSF, San Francisco, CA, USA Cellular and Molecular Biology, Goteborg University, Goteborg, CA, USA * Corresponding author; email: dfelsher{at}stanford.edu. The targeted inactivation of oncogenes may be a specific and effective treatment for cancer. However, since human cancers are the consequence of multiple genetic changes, the inactivation of one oncogene may not be sufficient to cause sustained tumor regression. Moreover, cancers are genomically unstable and may readily compensate for the inactivation of a single oncogene. Here we confirm by Spectral Karyotypic Analysis that MYC-induced hematopoietic tumors are highly genetically complex and genomically unstable. Nevertheless, the inactivation of MYC alone was found to be sufficient to induce sustained tumor regression. After prolonged MYC inactivation, some tumors exhibited a distinct propensity to relapse. When tumors relapsed, they no longer required the overexpression of MYC, but instead had acquired novel chromosomal translocations. We conclude that even highly genetically complex cancers are reversible upon the inactivation of MYC, unless they acquire novel genetic alterations that can sustain a neoplastic phenotype. 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