High-throughput mutation profiling of primary and metastatic endometrial cancers identifies KRAS, FGFR2 and PIK3CA to be frequently mutated

• Published in: PloS one Vol. 7; no. 12; p. e52795
• Main Authors: Krakstad, Camilla, Birkeland, Even, Seidel, Danila, Kusonmano, Kanthida, Petersen, Kjell, Mjøs, Siv, Hoivik, Erling A, Wik, Elisabeth, Halle, Mari Kyllesø, Øyan, Anne M, Kalland, Karl-Henning, Werner, Henrica Maria Johanna, Trovik, Jone, Salvesen, Helga
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.12.2012; Public Library of Science (PLoS)
• Subjects: Aged; Biology; Biotechnology; Cancer; Cancer metastasis; Carcinoma; Carcinoma - genetics; Carcinoma - secondary; Care and treatment; Cell Line, Tumor; Class I Phosphatidylinositol 3-Kinases; Clinical medicine; Cluster Analysis; Development and progression; DNA Mutational Analysis; Endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium; Ethics; Female; Fibroblast growth factor receptor 2; Gene amplification; Gene Frequency; Gene mutation; Genes; Genetic aspects; Genetic Association Studies; Genetic Linkage; Genomics; Gynecology; High-Throughput Nucleotide Sequencing; Histology; Hospitals; Humans; K-Ras protein; Kinases; Lesions; Malignancy; Mass spectrometry; Medicine; Metastases; Metastasis; Mutation; Mutation, Missense; Obstetrics; Oligonucleotide Array Sequence Analysis; Patients; Phosphatidylinositol 3-Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Spectrometry; Transcriptome; Tumor cell lines; Tumors; Uterine cancer; Norway; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052795

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. 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. Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies.