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Chromosome 3p plays an important role in tumorigenesis in many cancers, including nasopharyngeal carcinoma (NPC). We have previously shown chromosome 3p can suppress tumor growthin vivoby using the monochromosome transfer approach, which indicated the chromosome 3p21.3 region was critical for tumor suppression.BLU/ZMYND10is one of the candidate tumor suppressor genes mapping in the 3p21.3 critical region and is a candidate TSG for NPC. By quantitative RT-PCR, it is frequently downregulated in NPC cell lines (83%) and NPC biopsies (80%). However, no functional studies have yet verified the functional role ofBLU/ZMYND10as a tumor suppressor gene. In the current study, a gene inactivation test (GIT) utilizing a tetracycline regulation system was used to study the functional role ofBLU/ZMYND10. WhenBLU/ZMYND10is expressed in the absence of doxycycline, the stable transfectants were able to induce tumor suppression in nude mice. In contrast, downregulation ofBLU/ZMYND10in these tumor suppressive clones by doxycycline treatment restored the tumor formation ability. This study provides the first significant evidence to demonstrateBLU/ZMYND10can functionally suppress tumor formationin vivoand is, therefore, likely to be one of the candidate tumor suppressor genes involved in NPC. Published 2006 Wiley-Liss, Inc.