KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

Auner, Veronika; Kriegshäuser, Gernot; Tong, Dan; Horvat, Reinhard; Reinthaller, Alexander; Mustea, Alexander; Zeillinger, Robert

doi:10.1186/1471-2407-9-111

Cited by 79 publications

(53 citation statements)

References 23 publications

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“…In ovarian cancer, KRAS is more frequently mutated in MC (10-71%), than in NMC (2-25%, supplementary material, Figure S3) [110][111][112][113][114][115][116][117][118][119]. BRAF mutations are rare in ovarian carcinoma, with only 0-9% of MC and 0-4% of NMC showing this mutation [112,117,118].…”

Section: Mucinous Ovarian Carcinomamentioning

confidence: 99%

The molecular background of mucinous carcinoma beyond MUC2

Hugen

Simons²,

Halilović³

et al. 2014

Clin J Pathol

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The increasing interest of the oncology community in tumour classification and prediction of outcome to targeted therapies has put emphasis on an improved identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a subtype that is characterized by the presence of abundant extracellular mucin that comprises at least 50% of the tumour volume and is found in 10-15% of colorectal cancer patients. MC development is poorly understood, however, the distinct clinical and pathological presentation of MC suggests a deviant development and molecular background. In this review we identify common molecular and genetic alterations in colorectal MC. MC is characterized by a high rate of MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and PI3K/AKT pathways are significantly higher in MC compared with non-mucinous adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of microsatellite instability and is more frequently of the CpG island methylator phenotype. Although the majority of MCs arise from the large intestine, this subtype also develops in other organs, such as the stomach, pancreas, biliary tract, ovary, breast and lung. We compared findings from colorectal MC with tumour characteristics of MCs from other organs. In these organs, MCs show different mutation rates in the RAS/RAF/MAPK and PI3K/ AKT pathways as well, but a common mucinous pathway cannot be identified. Identification of conditions and molecular aberrations that are associated with MC generates insight into the aetiology of this subtype and improves understanding of resistance to therapies.

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Section: Mucinous Ovarian Carcinomamentioning

confidence: 99%

The molecular background of mucinous carcinoma beyond MUC2

Hugen

Simons²,

Halilović³

et al. 2014

Clin J Pathol

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“…KRAS mutations are the most common genetic event in 50% of mucinous borderline tumors and in 60% of primary MuOCs 8, 9, 10, 11, 1213.…”

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confidence: 99%

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Liew

Huang

Weng

et al. 2018

Intl Journal of Cancer

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Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor survival outcome in recurrent and advanced stages. The role of type‐specific epigenomics and its clinical significance remains uncertain. We analyzed the methylomic profiles of 6 benign mucinous adenomas, 24 MuOCs, 103 serous type of epithelial ovarian cancers (SeOCs) and 337 nonepithelial ovarian cancers. MuOC and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of which exhibited low methylation in MuOC and were associated with the response to glucocorticoid, ATP hydrolysis‐coupled proton transport, proteolysis involved in the cellular protein catabolic process and ion transmembrane transport. Hierarchical clustering analysis showed that the profiles of MuOC were similar to colorectal adenocarcinoma and stomach adenocarcinoma. Genetic interaction network analysis of differentially methylated genes in MuOC showed a dominant network module is the proteasome subunit beta (PSMB) family. Combined functional module and methylation analysis identified PSMB8 as a candidate marker for MuOC. Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian tumors (mucinous adenoma, MuOC or SeOC) and 62 samples of gastrointestinal cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples, predominantly as strong cytoplasmic and occasionally weak nuclei staining, but was not expressed in SeOC samples. Carfilzomib, a second‐generation proteasome inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous‐type‐specific methylation profile and suggests the potential use of a proteasome inhibitor to treat MuOC.

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“…KRAS, BRAF, or ERBB2 mutations have been reported in SBT (40,41). MMBT also showed KRAS mutations (46,48). Wnt signaling dysregulation has been suggested to play a role in ESS tumorigenesis (65).…”

Section: Discussionmentioning

confidence: 99%

“…There was reactivity for cytokeratin (CK)7, but not CK20 (47). KRAS mutations were detected in exon 1 and codon 12 in 69% of cases (46,48). No PTEN mutation was identified in any of the nine exons and PTEN immunoreactivity was diffuse in the nuclei of epithelial and underlying stromal cells (46).…”

Section: Müllerian Mucinous Borderline Tumormentioning

confidence: 99%

Identification of multiple pathways involved in the malignant transformation of endometriosis (Review)

et al. 2012

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Abstract. The association between endometriosis and malignant transformation has often been described in the medical literature. A search was conducted between 1966 and 2010 through the English language literature (online Medline PubMed database) using the keywords endometriosis combined with malignant transformation. The search revealed an increase in reports describing endometriosis and malignancy. Approximately 1.0% of women with endometriosis have lesions that undergo malignant transformation. The malignant processes that are associated with endometriosis may be classified into three groups: i) epithelial ovarian cancers (endometrioid adenocarcinoma and clear cell carcinoma), ii) other Müllerian-type tumors, including Müllerian-type mucinous borderline tumor and serous borderline tumor and iii) sarcomas such as adenosarcoma and endometrial stromal sarcoma in the female pelvic cavity. Persistent oxidative stress induced by endometriosis-dependent hemorrhage may be associated with carcinogenesis. In conclusion, the malignant transformation of endometriosis has multiple pathways of development and may share a common pathogenic mechanism; iron-induced oxidative stress derived from repeated hemorrhage.

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KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

Cited by 79 publications

References 23 publications

The molecular background of mucinous carcinoma beyond MUC2

The molecular background of mucinous carcinoma beyond MUC2

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

Identification of multiple pathways involved in the malignant transformation of endometriosis (Review)

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