Mutation analysis by whole exome sequencing of endometrial hyperplasia and carcinoma in one patient: Abnormalities of polymerase epsilon and the phosphatidylinositol-3 kinase pathway

J Obstet Gynaecol Res. 2018 Jan;44(1):179-183. doi: 10.1111/jog.13459. Epub 2017 Oct 6.

Abstract

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.

Keywords: endometrial carcinoma; endometrial hyperplasia; polymerase epsilon; ultra-mutated type; whole exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • DNA-Directed DNA Polymerase / genetics*
  • Endometrial Hyperplasia / genetics*
  • Endometrial Neoplasms / genetics*
  • Exome Sequencing / methods*
  • Female
  • Humans
  • Mutation
  • Signal Transduction / genetics*

Substances

  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • DNA-Directed DNA Polymerase