High-throughput mutation profiling of primary and metastatic endometrial cancers identifies KRAS, FGFR2 and PIK3CA to be frequently mutated
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...
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Published in | PloS one Vol. 7; no. 12; p. e52795 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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27.12.2012
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Abstract | 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. |
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AbstractList | 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. 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. 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. 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. BACKGROUNDDespite 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 FINDINGSWe 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/SIGNIFICANCEOur results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies. |
Audience | Academic |
Author | Mjøs, Siv Seidel, Danila Wik, Elisabeth Werner, Henrica Maria Johanna Trovik, Jone Kusonmano, Kanthida Salvesen, Helga Hoivik, Erling A Øyan, Anne M Halle, Mari Kyllesø Birkeland, Even Kalland, Karl-Henning Krakstad, Camilla Petersen, Kjell |
AuthorAffiliation | 2 Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway 5 Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany 8 Department of Microbiology, Haukeland University Hospital, Bergen, Norway 1 Department of Clinical Medicine, University of Bergen, Bergen, Norway 6 Computational Biology Unit, Uni Computing, Uni Research AS, Bergen, Norway 7 The Gade Institute, University of Bergen, Bergen, Norway 4 Max Planck Institute for Neurological Research, Cologne, Germany Peter MacCallum Cancer Centre, Australia 3 Department of Translational Genomics, University of Cologne, Cologne, Germany |
AuthorAffiliation_xml | – name: 3 Department of Translational Genomics, University of Cologne, Cologne, Germany – name: 7 The Gade Institute, University of Bergen, Bergen, Norway – name: 4 Max Planck Institute for Neurological Research, Cologne, Germany – name: 5 Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln – Bonn, University of Cologne, Cologne, Germany – name: 1 Department of Clinical Medicine, University of Bergen, Bergen, Norway – name: 6 Computational Biology Unit, Uni Computing, Uni Research AS, Bergen, Norway – name: Peter MacCallum Cancer Centre, Australia – name: 2 Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway – name: 8 Department of Microbiology, Haukeland University Hospital, Bergen, Norway |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: CK EB HBS. Performed the experiments: CK EB DS SM EAH MKH AMØ. Analyzed the data: CK EB SM EAH KK EW HBS. Contributed reagents/materials/analysis tools: KP MKH KHK HMJW JT. Wrote the paper: CK EB DS HBS. |
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Snippet | Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic... Background Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with... BACKGROUNDDespite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with... Background Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with... |
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Title | High-throughput mutation profiling of primary and metastatic endometrial cancers identifies KRAS, FGFR2 and PIK3CA to be frequently mutated |
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