title: Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations.
abstract: The targeted inactivation of oncogenes may be a specific and effective treatment for cancer. However, because 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 acquired novel chromosomal translocations. We conclude that even highly genetically complex cancers are reversible on the inactivation of MYC, unless they acquire novel genetic alterations that can sustain a neoplastic phenotype.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University, CA 94305, USA.
authors.forename: Asa
authors.initials: A
authors.lastname: Karlsson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giuriato
authors.forename: Flora
authors.initials: F
authors.lastname: Tang
authors.forename: Jingly
authors.initials: J
authors.lastname: Fung-Weier
authors.forename: Göran
authors.initials: G
authors.lastname: Levan
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D020732:Cytogenetic Analysis; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D008223:Lymphoma / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D051379:Mice; D012008:Recurrence; D014178:Translocation, Genetic; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D004318:Doxycycline