Abstract
Background:
Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic endometrial carcinoma. In order to improve treatment, underlying molecular characteristics of primary and metastatic disease must be explored.
Methodology/principal findings:
We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in endometrial cancer. 67 primary tumors, 15 metastases corresponding to 7 of the included primary tumors and 11 endometrial cancer cell lines were screened for point mutations in 28 known oncogenes. We found that 27 (40.3%) of 67 primary tumors harbored one or more mutations with no increase in metastatic lesions. FGFR2, KRAS and PIK3CA were consistently the most frequently mutated genes in primary tumors, metastatic lesions and cell lines.
Conclusions/significance:
Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Carcinoma / genetics*
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Carcinoma / secondary
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Cell Line, Tumor
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Class I Phosphatidylinositol 3-Kinases
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Cluster Analysis
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DNA Mutational Analysis
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Endometrial Neoplasms / genetics*
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Endometrial Neoplasms / pathology
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Female
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Gene Frequency
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Genetic Association Studies
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Genetic Linkage
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High-Throughput Nucleotide Sequencing
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Humans
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Mutation, Missense
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Oligonucleotide Array Sequence Analysis
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Phosphatidylinositol 3-Kinases / genetics*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins p21(ras)
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Receptor, Fibroblast Growth Factor, Type 2 / genetics*
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Transcriptome
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ras Proteins / genetics*
Substances
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KRAS protein, human
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Proto-Oncogene Proteins
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Phosphatidylinositol 3-Kinases
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Class I Phosphatidylinositol 3-Kinases
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PIK3CA protein, human
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FGFR2 protein, human
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Receptor, Fibroblast Growth Factor, Type 2
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Proto-Oncogene Proteins p21(ras)
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ras Proteins
Grants and funding
The Western Norway Regional Health Authority (grant number: 911351 and 911624), Norwegian Research Council (grant number: 193373 and 205404), and The Norwegian Cancer Society (grant number: 628837). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.