Identification of nonsynonymous TP53 mutations in hydatidiform moles

Mutat Res. 2018 May:809:20-23. doi: 10.1016/j.mrfmmm.2018.03.006. Epub 2018 Mar 29.

Abstract

Hydatidiform mole (HM), an unusual pregnancy with pure or predominant paternal genetic contribution, is the most common form of gestational trophoblastic disease. Most HM regress after uterine evacuation but some will develop into persistent disease or even frank malignancy. Although p53 is highly expressed in HM, TP53 mutations have rarely been detected in previous studies. Here we screened for specific missense mutations on several TP53 hotspots in 49 HMs using a highly sensitive pyrosequencing approach and revealed the significant existence of such mutations in HM tissues. A particularly high frequency (∼59% of the cases) of p53 inactivating mutation on exon 7 has been detected. Our identification of hitherto unreported TP53 mutations in HM suggests the presence of p53 mutants and reflects the advantages of using pyrosequencing for point mutation detection in clinical samples. Traditional sequencing method may have overlooked such mutations that only occur in a small population of trophoblasts.

Keywords: Hydatidiform mole; Pyrosequencing; TP53 mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • Female
  • Humans
  • Hydatidiform Mole / genetics*
  • Hydatidiform Mole / metabolism
  • Hydatidiform Mole / pathology
  • Point Mutation*
  • Pregnancy
  • Retrospective Studies
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53