The gene encoding the methionine salvage pathway methylthioadenosine phosphorylase (MTAP) is a tumor suppressor gene that is frequently inactivated in a wide variety of human cancers. Loss of MTAP is associated with elevated expression of ornithine decarboxylase (ODC), a key enzyme in the synthesis of polyamines and a known oncogene. Here, we have examined if heterozygosity for a null mutation in Mtap could accelerate tumor development in two different mouse cancer models, Eα-myc transgenic and Pten+/−. We found that the median age of tumor formation in both models was significantly accelerated in Mtap+/− compared to Mtap+/+ mice. In Eα-myc mice, Mtap mutations accelerated the formation of lymphomas from cells in the early pre-B stage and these tumors tended to be of higher grade and have higher expression levels of ODC protein compared to those observed in control Emu-myc Mtap+/+ mice. Supprisingly, examination of Mtap mRNA and protein in highly lymphoma infiltrated tissue in heterozygous animals indicates that >80% of the tumors maintain expression of the Mtap allele. Our findings show that germline inactivation of a single Mtap allele enhances lymphomagenesis in both Emu-myc and Pten+/− mice and is associated with elevated levels of ODC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2173. doi:1538-7445.AM2012-2173