These data suggest that TYMS expression in histiocytic/monocytic hematopoietic cells lacking Ink4a/Arf induces double strand DNA damage that leads to the acquisition of structural and numerical chromosomal changes and genomic instability that may be a contributing factor to enhancement of tumor progression in hTS/Ink4a/Arf−/− mice. The gene discussed is CDKN2A; the disease is neoplasm.