Miyamoto Tsutomu, Ando Hirofumi, Asaka Ryoichi, Yamada Yasushi, Shiozawa Tanri
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
J Obstet Gynaecol Res. 2018 Jan;44(1):179-183. doi: 10.1111/jog.13459. Epub 2017 Oct 6.
In order to understand the role of gene mutations in endometrial carcinogenesis, whole exome sequencing via laser microdissection was performed in the normal endometrium, atypical endometrial hyperplasia and endometrial carcinoma in the same patient. A total of 4046 and 5746 mutations with amino acid substitution were detected in endometrial hyperplasia and endometrial carcinoma, respectively; 2252 were common in both tissues and might play crucial roles in early carcinogenesis. These common mutations included polymerase epsilon (POLE) and DNA mismatch repair (MMR) genes, indicating that an ultra-mutated phenotype, and also included PTEN and PIK3CA. The mutation-prone environment evoked by mutations in the POLE and MMR genes associated with the activated phosphatidylinositol-3 kinase pathway played a pivotal role in this case.
为了解基因突变在子宫内膜癌发生中的作用，对同一患者的正常子宫内膜、非典型子宫内膜增生和子宫内膜癌进行了激光显微切割全外显子测序。在子宫内膜增生和子宫内膜癌中分别检测到4046个和5746个氨基酸替代突变；2252个突变在两种组织中都存在，可能在早期致癌过程中起关键作用。这些常见突变包括聚合酶ε（POLE）和DNA错配修复（MMR）基因，表明存在超突变表型，还包括PTEN和PIK3CA。POLE和MMR基因的突变引发的易突变环境与激活的磷脂酰肌醇-3激酶途径相关，在该病例中起关键作用。
