title: High throughput interrogation of somatic mutations in high grade serous cancer of the ovary.
abstract: BACKGROUND
  Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology.
  
  
  RESULTS
  The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%).
  
  
  CONCLUSIONS
  Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. Ursula_matulonis@dfci.harvard.edu
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: Michelle
authors.initials: M
authors.lastname: Hirsch
authors.forename: Emanuele
authors.initials: E
authors.lastname: Palescandolo
authors.forename: Eejung
authors.initials: E
authors.lastname: Kim
authors.forename: Joyce
authors.initials: J
authors.lastname: Liu
authors.forename: Paul
authors.initials: P
authors.lastname: van Hummelen
authors.forename: Laura
authors.initials: L
authors.lastname: MacConaill
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
mesh_terms: D000483:Alleles; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*
chemical_list: D017931:DNA Primers; D066246:ErbB Receptors