Dataset Information

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

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.

SUBMITTER: Krakstad C

PROVIDER: S-EPMC3531332 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Krakstad Camilla C Birkeland Even E Seidel Danila D Kusonmano Kanthida K Petersen Kjell K Mjøs Siv S Hoivik Erling A EA Wik Elisabeth E Halle Mari Kyllesø MK Øyan Anne M AM Kalland Karl-Henning KH Werner Henrica Maria Johanna HM Trovik Jone J Salvesen Helga H

PloS one 20121227 12

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in end ...[more]

PMID: 23300780

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Project description:BRAF and KRAS genes are known to play a similar role in the activation of RAS-RAF-MEK-ERK signaling pathway in colorectal tumorigenesis. However, BRAF-mutated colorectal cancers (CRCs) have distinct clinicopathologic characteristics different from those of the KRAS mutated ones as in comparison the BRAF-mutated CRCs are associated with a much worse prognosis for the afflicted patients. This study aimed to determine the different miRNA expression signatures associated with BRAF-mutated CRCs in comparison to KRAS-mutated ones, and to identify the specific miRNAs possibly mediating the aggressive phenotype of the BRAF-mutated CRCs. We screened 535 formalin-fixed paraffin-embedded CRC tissue samples for the BRAF V600E mutation, and selected 7 BRAF-mutated and 7 KRAS-mutated CRCs that were tumor size, stage, and microsatellite status-matched. Affymetrix GeneChip® miRNA 4.0 Array was used for detection of miRNA expression differences in the selected samples. We validated the array results by quantitative reverse transcription polymerase chain reaction (qRT-PCR) for selected miRNAs. A total of 10 differentially expressed (DE) miRNAs associated with BRAF-mutated CRCs were obtained, including miR-31-5p, miR-877-5p, miR-362-5p, and miR-425-3p. miR-31-5p showed the highest fold change (8.3-fold) among all of the miRNAs analyzed. From the analyses of GO biological processes, the DE-miRNAs were functionally relevant to cellular proliferation such as positive regulation of gene expression (P?=?1.26?×?10(-10)), transcription (P?=?9.70?×?10(-10)), and RNA metabolic process (P?=?1.97?×?10(-9)). Bioinformatics analysis showed that the DE-miRNAs were significantly enriched in cancer-associated pathways including neutrophin signaling (P?=?6.84?×?10(-5)), pathways in cancer (P?=?0.0016), Wnt signaling (P?=?0.0027), and MAPK signaling pathway (P?=?0.0036). Our results suggest that the DE-miRNAs in BRAF-mutated CRCs in comparison to KRAS-mutated CRCs are implicated in the aggressive phenotype of the BRAF-mutated CRCs. Further experimental validation is required to confirm these results.

Dataset Information

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

Background

Methodology/principal findings

Conclusions/significance

Publications

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

Similar Datasets

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