Detection of SRSF2-P95 Mutation by High-Resolution Melting Curve Analysis and Its Effect on Prognosis in Myelodysplastic Syndrome

作者：Lin, Jiang; Yang, Jing; Wen, Xiang-mei; Yang, Lei; Deng, Zhao-qun; Qian, Zhen; Ma, Ji-chun; Guo, Hong; Zhang, Ying-ying; Qian, Wei^*; Qian, Jun

来源：PLos One, 2014, 9(12): e115693.

DOI：10.1371/journal.pone.0115693

• ACUTE MYELOID-LEUKEMIA
• SPLICEOSOMAL MACHINERY
• SPLICING MACHINERY
• PATHWAY
• SF3B1
• IMPACT
• U2AF1

Hotspot mutations of serine/arginine-rich splicing factor 2 (SRSF2) gene have been identified in a proportion of hematologic malignancies including myelodysplastic syndrome (MDS). The aim of the present study was to develop a new approach to screen SRSF2 mutation and analyze the clinical relevance of SRSF2 mutations in Chinese MDS. A protocol based on high-resolution melting analysis (HRMA) was established to screen SRSF2-P95 mutation in 108 MDS patients and was compared with Sanger sequencing. The clinical relevance of SRSF2 mutations was further evaluated. HRMA identified five (4.6%) cases with SRSF2 mutation, completely validated by Sanger sequencing without false positive or negative results. The sensitivities of HRMA and Sanger sequencing were 10% and 25% for the detection of SRSF2-P95H mutation, respectively, against the background of wild-type DNA. Patients with SRSF2 mutation had shorter overall survival time than those with wild-type SRSF2 in both the whole cohort of cases and those with normal karyotype (P=0.069 and 0.023, respectively). Multivariate analysis confirmed SRSF2 mutation as an independent risk factor in both patient populations. We established a fast, high-throughput, and inexpensive HRMA-based method to screen SRSF2 mutation, which could be used in clinical diagnostic laboratories. SRSF2 mutations were significantly associated with mortality rate in the MDS affected Chinese.

• 出版日期2014-12-26
• 单位江苏大学