Detection of mitochondrial DNA mutations in gestational trophoblastic disease

Hum Mutat. 2003 Aug;22(2):177. doi: 10.1002/humu.9160.


Mitochondrial DNA (mtDNA) mutations have been implicated in a wide range of human disease. However, its role in gestational trophoblastic disease remains unclear. In this study, the entire mitochondrial genome of 10 hydatidiform moles (HM) and one choriocarcinoma were examined by automated DNA sequencing after amplification by polymerase chain reaction. MtDNA sequences obtained separately from disease tissues (HM and choriocarcinoma) and patients' tissues were compared. Of the 133 neutral sequence variants identified, 41 have not been reported to date. Large or small-scale deletion or insertion was not detected in any of the samples studied. A total of six (five in the D-loop and one in the 16S rRNA gene) somatic point mutations were detected in the choriocarcinoma sample, in contrast to none being detected in the HM samples. Somatic mtDNA instability was detected in the D-loop region in three cases of HM as well as in the choriocarcinoma sample. Somatic mtDNA instability appeared in the same nucleotide position, from 303 to 309, within the Conserved Sequence Block II resulting in alteration in length of the homopolymorphic C-tract, reflecting microsatellite instability. The results suggest that mtDNA instability may be an early event occurring at a premalignant stage. Occurrence of multiple somatic mtDNA mutations in choriocarcinoma suggests that mtDNA mutations might play an important role in the molecular pathogenesis of invasive gestational trophoblastic disease.

MeSH terms

  • Choriocarcinoma / genetics
  • DNA, Mitochondrial / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Gestational Age
  • Gestational Trophoblastic Disease / genetics*
  • Humans
  • Hydatidiform Mole / genetics
  • Mutation / genetics*
  • Pregnancy
  • Pregnancy Complications, Neoplastic / pathology
  • Pregnancy Trimester, Third / genetics


  • DNA, Mitochondrial
  • DNA, Neoplasm