Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas

J Natl Cancer Inst. 2016 Feb 1;108(6):djv427. doi: 10.1093/jnci/djv427. Print 2016 Jun.


Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Ovarian Epithelial
  • Clone Cells*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Mutational Analysis / methods
  • DNA, Neoplasm / analysis*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Exome
  • Female
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Microsatellite Instability
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology


  • DNA, Neoplasm