Evaluation of EGFR, KRAS and BRAF gene mutations in renal cell carcinoma

Bayrak, Ömer; Şen, Haluk; Bulut, Ersan; Cengiz, Beyhan; Karakök, Metin; Erturhan, Sakıp; Şeçkiner, İlker

doi:10.15586/jkcvhl.2014.10

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…Maybe it is because PIK3CA mutations are rare in ccRCC and are present only in 2-5% of tumors [46] or result from intratumoral molecular heterogeneity which should be studied by novel sampling strategies [47]. Similarly to other authors [47][48][49][50] we also did not detect mutations in KRAS gene. It seems that mutations in PIK3CA and KRAS are not significant events in the development of ccRCC.…”

Section: Emt In Localized Ccrccsupporting

confidence: 70%

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Gasińska

Jaszczyński

Adamczyk

et al. 2019

Folia Histochem Cytobiol.

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Introduction. It has been suggested that the metastatic potential of neoplastic cells can be predicted on the basis of their biological features, including expression of proteins involved in the epithelial to mesenchymal transition (EMT). Therefore, the purpose of this work was to (1) evaluate the expression of EMT markers: ZEB2, vimentin, N-cadherin, TWIST, PTEN, survivin, E-cadherin, Ki-67 and GLUT-1, (2) assess mutation status of two genes: PIK3CA and KRAS, and (3) investigate the potential relationships between the studied biomarkers and clinicopathological factors in clear-cell renal cell carcinoma (ccRCC). Material and methods. Tumor tissue samples (embedded in paraffin blocks) from 159 patients undergoing radical nephrectomy were analyzed. Proteins expression was evaluated immunohistochemically. DNA mutations were analyzed on DNA isolated from tumor tissue and amplified by real-time PCR detection using suitable fluorescent labeled TaqMan assays. Results. One hundred and seven men and 52 women of mean age of 63.1years were enrolled. Fifty four cancers at pTNM stage I-II and 98 at pTNM III-IV stage were diagnosed. There were 30 Fuhrman grade G1, 61 Fuhrman G2, 49 Fuhrman G3 and 19 Fuhrman G4 tumors. A negative correlation between ZEB2 (p = 0.047, r = -0.172) or E-cadherin expression (p = 0.027, r = -0.191) and TNM was observed. Positive association between grade and Ki-67 (p < 0.001), survivin (p < 0.001), vimentin (p < 0.001) immunoreactivity and negative association between TWIST expression (p = 0.029) or PTEN expression (p = 0.013) were found. Ki-67 expression was positively correlated with survivin (p < 0.001, r = 0.617), vimentin (p = 0.001, r = 0.251) and N-cadherin (p = 0,009, r = 0.207) immunoreactivity which can suggest tumor aggressiveness. TWIST was negatively correlated with E-cadherin (p < 0.001, r = -0.284), vimentin (p < 0.001, r = -0.297) and N-cadherin (p < 0.002, r = -0.241). ZEB2 was not associated with ccRCC grade but was negatively correlated with E-cadherin (p = 0.055, r= -0.153) and PTEN (p = 0.006). GLUT-1 expression was inversely linked to E-cadherin expression (p = 0.022, r= -0.182). Mutations in PIK3CA and KRAS genes were not found in any of the studied ccRCC tumors. Conclusions. Low-grade tumors showed higher expression of ZEB2 and TWIST proteins than high-grade tumors, which can suggest that EMT in ccRCC begins at early stages of tumor development and, therefore, evaluation of these proteins, together with other biomarkers, may be useful for assessment of the tumor metastatic potential.

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Section: Emt In Localized Ccrccsupporting

confidence: 70%

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Gasińska

Jaszczyński

Adamczyk

et al. 2019

Folia Histochem Cytobiol.

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“…Previous studies using NGS have revealed the occurrence of evolutionary convergent phenotypic events, despite divergent genotypic alterations, in genes related to cRCC pathogenesis, including distinct mutations in genes involved in the PI3K-AKT-mTOR pathway, chromatin remodeling, and the VHL-HIF pathway (Voss et al, 2014; Riazalhosseini and Lathrop, 2016). Studies have also shown that the EGFR protein is overexpressed in both primary and metastatic RCC (Bayrak et al, 2014).…”

Section: Molecular Signatures Of Oeff Specimens Tested By Ocav1mentioning

confidence: 99%

“…Regions prone to high systematic errors can be defined based on technical limitations of an NGS platform and validation data. For instance, variants in homopolymer regions, genes with high homology to pseudogenes or within repetitive regions are some of the sources for systematic errors (Bragg et al, 2013; Bayrak et al, 2014; Damiati et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Validation and Clinical Applications of a Comprehensive Next Generation Sequencing System for Molecular Characterization of Solid Cancer Tissues

Dehghani

Rosenblatt

et al. 2019

Front. Mol. Biosci.

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Identification of somatic molecular alterations in primary and metastatic solid tumor specimens can provide critical information regarding tumor biology and its heterogeneity, and enables the detection of molecular markers for clinical personalized treatment assignment. However, the optimal methods and target genes for clinical use are still being in development. Toward this end, we validated a targeted amplification-based NGS panel (Oncomine comprehensive assay v1) on a personal genome machine sequencer for molecular profiling of solid tumors. This panel covers 143 genes, and requires low amounts of DNA (20 ng) and RNA (10 ng). We used 27 FFPE tissue specimens, 10 cell lines, and 24 commercial reference materials to evaluate the performance characteristics of this assay. We also evaluated the performance of the assay on 26 OCT-embedded fresh frozen specimens (OEFF). The assay was found to be highly specific (>99%) and sensitive (>99%), with low false-positive and false-negative rates for single-nucleotide variants, indels, copy number alterations, and gene fusions. Our results indicate that this is a reliable method to determine molecular alterations in both fixed and fresh frozen solid tumor samples, including core needle biopsies.

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“…The same situation has been observed in renal cell carcinomas. Hence, KRAS mutations do not appear to play a major role in these types of tumors [13], but several studies have revealed that KRAS overexpression is a frequent event in these tumors [14]. Here, restoration of miR-216b inhibits KRAS protein level in ccRCC cells (Fig.…”

Section: Discussionmentioning

confidence: 92%

miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma

Wang

Dong

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. Methods: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. Results: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3’untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. Conclusion: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.

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Evaluation of EGFR, KRAS and BRAF gene mutations in renal cell carcinoma

Cited by 16 publications

References 18 publications

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Validation and Clinical Applications of a Comprehensive Next Generation Sequencing System for Molecular Characterization of Solid Cancer Tissues

miR-216b Post-Transcriptionally Downregulates Oncogene KRAS and Inhibits Cell Proliferation and Invasion in Clear Cell Renal Cell Carcinoma

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