肿瘤特异的融合基因是理想的分子诊断标志和治疗靶标，如BCR-ABL及EML-ALK。近来发现染色体重排产生的融合基因不仅在血液肿瘤及软组织肉瘤发生中起关键作用，而在部分上皮性癌中也可能起驱动作用。我们通过高通量转录组测序（RNA-seq）和生物信息学分析，在鼻咽癌细胞株C666-1中发现新的融合基因AARS-MADx。前期研究表明AARS-MADx具有肿瘤特异性，在高达16% (32/200)鼻咽癌标本中检测到其mRNA，AARS-MADx编码-37KD蛋白，外源性表达可诱导癌细胞出现基因组不稳定性表型如微核和双核的形成，并增强癌细胞克隆形成能力。因此，本项目将明确鼻咽癌组织中AARS-MADx基因融合（FISH检测）和内源性的蛋白表达（IHC或O-LINK）并探讨其临床意义，阐明AARS-MADx诱导基因组不稳定性及其致癌机制，为发展AARS-MADx作为鼻咽癌分型和治疗靶标提供依据。

Highly recurrent and cancer specific fusion genes have defined distinct molecular subtypes linked to unique clinicopathological features and become ideal drug targets. Fusion genes resulting from chromosomal rearrangements are critically involved in the molecular pathogenesis not only of hematological malignancies and sarcomas, but also of epithelial cancers. To screen and characterization fusion genes in nasopharyngeal carcinomas (NPC), we performed whole-transcriptome analysis by paired-end sequencing (RNA-seq) and discovered a novel fusion gene AARS-MADx in a NPC cell line C666. In the subsequent evaluation, we demonstrated that this fusion gene was recurrently occurred in NPC samples with up to 16% positive rate in 32/200 samples detected. AARS-MADx fusion gene encoded a 37 KD protein. As functional consequences, overexpression of AARS-MADx fusion gene could induce genomic instability such as increase number of micronuclei and enhance the colony formation ability of tumor cells .Thus, we propose to further identify the fusion events at chromosome level by FISH, to detect the endogenous protein level by IHC or O-Link methods in NPC cell lines and biopsies as well as the potential clinical significance in AARS-MADx positive samples, and to characterize the molecular mechanism of AARS-MADx on genomic instability and tumorigenesis of NPC. Our results will provide a molecular basis for further development of molecular diagnosis and therapy by targeting AARS-MADx in NPC.