错配切除修复蛋白1（ERCC1）是DNA修复蛋白，可与XPF形成异二聚体，有效地清除DNA损伤。我们在人肿瘤细胞中发现了一个新的ERCC1剪切变异体，起始于正常转录起始位点上游，是顺铂诱导表达的主要ERCC1转录本，其功能可能与顺铂获得性耐药相关(oncogene,2012)。基于此，本课题的研究目标和内容包括：1.进一步明确新ERCC1剪切变异体的核苷酸序列；2.从临床病理标本和细胞模型两方面阐述ERCC1剪切变异体对卵巢癌顺铂耐药的影响；3.探讨ERCC1新剪切变异体与卵巢癌发生的相关性； 4.分析新ERCC1剪切变异体的转录调控机制，探索新ERCC1启动子。本课题的研究成果将为解决顺铂获得性耐药问题提供新的思路，新ERCC剪切变异体或能成为卵巢癌的临床生物标记，这对卵巢癌诊断有重要意义。

ERCC1 is DNA repair gene which form complex with XPF to remove cisplatin induced DNA damage and cause chemotherapy resistance. We preliminary found a novel ERCC1 mRNA initiated upstream of the normal transcription initiation site and strongly regulated by cisplatin. We wish to further investigate the sequence of this novel transcript and characterize its roles in cisplatin resistance and ovarian cancer progression. Furthermore, we propose to identify the promoter of this novel ERCC1 transcript. In this study, we show the sequence of this novel ERCC1 transcript, unravel the roles of different ERCC1 transcript in ciplatin resistance and cancer development.