背景:成熟的卵巢囊性畸胎瘤是最常见的生殖细胞肿瘤类型,占卵巢肿瘤的33%。研究这些肿瘤可能会更好地了解其逐步发育过程和分子基础,并为组织工程技术的发展提供有用的信息。
方法:在本研究中,通过全外显子组测序分析了9个成熟的卵巢囊性畸胎瘤,并将结果与癌症和dbSNP数据库中的体细胞突变目录进行了比较。
结果:在15个基因中验证了突变,所有9个(100%)样品中的突变和蛋白质编码的变化。前10个突变基因是FLG,MUC17,MUC5B,RP1L1,NBPF1,GOLGA6L2,SLC29A3,SGK223,PTGFRN,FAM186A此外,蛋白质编码变化的外显子中的7个变体可能在卵巢成熟囊性畸胎瘤的发展中很重要,即PTGFRN,DUSP5、MPP2、PHLDA1、PRR21、GOLGA6L2和KRTAP4-2。
结论:这些遗传改变可能在畸胎瘤形成中起重要的病因学作用。此外,在全外显子组测序中发现的DUSP5和PHLDA1基因的新突变可能有助于解释畸胎瘤的特征.
BACKGROUND: Mature cystic teratomas of the ovary are the most common type of germ cell tumor, comprising 33% of ovarian tumors. Studying these tumors may result in a better understanding of their stepwise developmental processes and molecular bases and provide useful information for the development of tissue-engineering technologies.
METHODS: In the present study, 9 mature cystic teratomas of the ovary were analyzed by whole-exome sequencing and the results were compared with the Catalogue of Somatic Mutations in Cancer and dbSNP databases.
RESULTS: Mutations were validated in 15 genes with alterations in all 9 (100%) samples and changes in protein coding. The top 10 mutated genes were FLG, MUC17, MUC5B, RP1L1, NBPF1, GOLGA6L2, SLC29A3, SGK223, PTGFRN, and FAM186A. Moreover, 7 variants in exons with changes in protein coding are likely of importance in the development of mature cystic teratomas of the ovary, namely PTGFRN, DUSP5, MPP2, PHLDA1, PRR21, GOLGA6L2, and KRTAP4-2.
CONCLUSIONS: These genetic alterations may play an important etiological role in teratoma formation. Moreover, novel mutations in DUSP5 and PHLDA1 genes found on whole-exome sequencing may help to explain the characteristics of teratomas.