Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencing-based diagnostic assay reveals new routes to targeted therapies

Gynecol Oncol. 2013 Sep;130(3):554-9. doi: 10.1016/j.ygyno.2013.06.019. Epub 2013 Jun 20.


Objective: Targeted next generation sequencing (NGS) was evaluated for its ability to identify unanticipated targetable genomic alterations (GA) for patients with relapsed ovarian epithelial carcinoma (OC).

Methods: DNA sequencing was performed for 3320 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer on indexed, adaptor ligated, hybridization-captured libraries using DNA isolated from FFPE sections from 48 histologically verified relapsed OC specimens. The original primary tumor was sequenced in 26 (54%) of the cases and recurrent/metastatic tumor site biopsies were sequenced in 22 (46%) of the cases. Actionability was defined as: GA that predict sensitivity or resistance to approved or standard therapies or are inclusion or exclusion criteria for specific experimental therapies in NCI registered clinical trials.

Results: There were 38 (80%) serous, 5 (10%) endometrioid, 3 (6%) clear cell, 1 mucinous (2%) and 1 (2%) undifferentiated carcinomas. 141 GA were identified with an average of 2.9 GA (range 0-8) per tumor, of which 67 were actionable for an average of 1.4 actionable GA per patient (range 0-5). 33/48 (69%) of OC patient samples harbored at least one actionable GA. Most common GA were TP53 (79%); MYC (25%); BRCA1/2 (23%); KRAS (16.6%) and NF1 (14.5%). One tumor featured an ERBB2 point mutation. One of 3 (33%) of clear cell tumors featured cMET amplification validated by both FISH and IHC.

Conclusions: NGS assessment of therapy resistant OC identifies an unexpectedly high frequency of GA that could influence targeted therapy selection for the disease.

Keywords: Deletion; Gene fusion; Mutation; Next generation sequencing; Ovarian cancer; Targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • DNA Fingerprinting
  • Drug Resistance, Neoplasm / genetics*
  • Exons / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genes, Neurofibromatosis 1
  • Genes, myc
  • Humans
  • Middle Aged
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Precision Medicine
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Sequence Analysis, DNA*
  • Tumor Suppressor Protein p53 / genetics
  • Young Adult
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins