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

Camilla Krakstad; Even Birkeland; Danila Seidel; Kanthida Kusonmano; Kjell Petersen; Siv Mjøs; Erling A Hoivik; Elisabeth Wik; Mari Kyllesø Halle; Anne M Øyan; Karl-Henning Kalland; Henrica Maria Johanna Werner; Jone Trovik; Helga Salvesen

doi:10.1371/journal.pone.0052795

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

PLoS One. 2012;7(12):e52795. doi: 10.1371/journal.pone.0052795. Epub 2012 Dec 27.

Authors

Camilla Krakstad¹, Even Birkeland, Danila Seidel, Kanthida Kusonmano, Kjell Petersen, Siv Mjøs, Erling A Hoivik, Elisabeth Wik, Mari Kyllesø Halle, Anne M Øyan, Karl-Henning Kalland, Henrica Maria Johanna Werner, Jone Trovik, Helga Salvesen

Affiliation

¹ Department of Clinical Medicine, University of Bergen, Bergen, Norway. camilla.krakstad@med.uib.no

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

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma / genetics*
Carcinoma / secondary
Cell Line, Tumor
Class I Phosphatidylinositol 3-Kinases
Cluster Analysis
DNA Mutational Analysis
Endometrial Neoplasms / genetics*
Endometrial Neoplasms / pathology
Female
Gene Frequency
Genetic Association Studies
Genetic Linkage
High-Throughput Nucleotide Sequencing
Humans
Mutation, Missense
Oligonucleotide Array Sequence Analysis
Phosphatidylinositol 3-Kinases / genetics*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins p21(ras)
Receptor, Fibroblast Growth Factor, Type 2 / genetics*
Transcriptome
ras Proteins / genetics*

Substances

KRAS protein, human
Proto-Oncogene Proteins
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
PIK3CA protein, human
FGFR2 protein, human
Receptor, Fibroblast Growth Factor, Type 2
Proto-Oncogene Proteins p21(ras)
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.