Abstract
BackgroundEpithelial 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.Methodology/Principal FindingsThe 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/SignificanceSequenom 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.
Highlights
Epithelial ovarian cancer is the most lethal of all of the gynecologic malignancies, and new treatments are needed for both newly diagnosed patients as well as patients with recurrent cancer [1]
Since OncoMap interrogates only a subset of TP53 mutations and does not detect deletion events, the observed frequency of TP53 alterations agrees with recent work from The Cancer Genome Atlas Project (TCGA) [10] that has confirmed the finding that TP53 mutations are the most common somatic mutation in high grade serous ovarian cancer (HGSC) cancers
Our group has demonstrated that somatic oncogene mutations can be detected in HGSC using a Sequenom based assay called OncoMap that uses DNA derived from formalin-fixed paraffin-embedded (FFPE) tissue
Summary
Epithelial ovarian cancer is the most lethal of all of the gynecologic malignancies, and new treatments are needed for both newly diagnosed patients as well as patients with recurrent cancer [1]. HGSC is the most common subtype and is associated with initial chemotherapy responsiveness when first diagnosed. Activating point mutations in proto-oncogenes have been observed in many human cancers, and such mutations can confer ‘oncogene addiction’ upon the relevant cancer cells [4]. This oncogene dependency provides a basis for targeting activated oncogenes in treatment as exemplified by the success of imatinib and erlotinib in cancers that harbor BCL-ABL and EGFR alterations, respectively. 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
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