T2093 Microsatellite Instability (MSI), Hmlh1 Promoter Hypermethylation and BRAF Mutation Analysis in Sporadic Colorectal Cancers (Crcs) of Different Ethnic Groups in Israel

Vilkin, Alex; Niv, Yaron; Nagasaka, Takeshi; Morgenstern, Sarah; Levi, Zohar; Fireman, Zvi; Li, Mei-Shu; Fuerst, Flory; Goel, Ajay; Boland, C. Richard

doi:10.1016/s0016-5085(08)62883-8

Cited by 8 publications

(10 citation statements)

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“…The prevalence of BRAF mutation was 28% in interval cancers compared to 19% in non-interval cancers, with an overall prevalence of 21% in the entire study population. This is similar to prevalence reported by others [1,2]. We also found BRAF and MSI overlap to be high (50%), as reported by others [4].…”

Section: Discussionsupporting

confidence: 92%

“…An activating mutation in the RAF gene, BRAF, leads to unregulated cell growth and tumor proliferation. Mutations of the BRAF gene have been reported in 9.5-23.5% of all sporadic colon cancers and are strongly associated with microsatellite instability (MSI) in sporadic colon cancers, but not in hereditary nonpolyposis colorectal cancer (HNPCC) [1,2]. BRAF mutation is seen in microsatellite stable tumors as well and patients with this combination have been associated with a worse prognosis (poorer survival) than patients with the BRAF mutation in conjunction with MSI [1].…”

Section: Introductionmentioning

confidence: 99%

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Is BRAF Mutation Associated with Interval Colorectal Cancers?

et al. 2010

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Is BRAF Mutation Associated with Interval Colorectal Cancers?

et al. 2010

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“…Examining tumor factors and clinical outcome is important in cancer research 35-39. Studies examining the relation between p-AKT expression and prognosis in human cancers have yielded variable results 7-12.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers

Baba

Nosho

Shima

et al. 2010

Cancer

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BACKGROUND: AKT (AKT1, AKT2, and AKT3) was a downstream effector of phosphatidylinositide-3-kinase (PI3K) and played crucial roles in protein synthesis, cellular metabolism, survival, and proliferation. The PI3K/AKT pathway was commonly activated in human cancers and was recognized as a potential target for anticancer therapy. Nonetheless, clinical, molecular, or prognostic features of AKT-activated colon cancer remained uncertain. METHODS: Using a database of 717 colon and rectal cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, Ser473 phosphorylated AKT (p-AKT) expression was detected in 448 (62%) tumors by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazards ratio (HR), adjusting for clinical and tumoral features, including PIK3CA, KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), LINE-1 methylation, TP53 (p53), and FASN (fatty acid synthase). RESULTS: Tumor p-AKT expression was associated with PIK3CA mutation (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12-2.80; P ¼ .015). p-AKT expression was significantly associated with longer colorectal cancer-specific survival in Kaplan-Meier analysis (log-rank P ¼ .0005), univariate Cox regression (HR, 0.62; 95% CI, 0.47-0.82; P ¼ .0006) and multivariate analysis (adjusted HR, 0.75; 95% CI, 0.56-0.99; P ¼ .048) adjusting for clinical and molecular variables including PIK3CA, MSI, CIMP and LINE-1 hypomethylation. p-AKT expression was inversely associated with high stage (III-IV) (adjusted OR, 0.63; 95% CI, 0.45-0.88, P ¼ .0071). CONCLUSIONS: p-AKT expression in colorectal cancer is associated with low stage and good prognosis. p-AKT may serve as a tissue biomarker to identify patients with superior prognosis and a possible therapeutic target (analogous to estrogen receptor ESR1 in breast cancer). Cancer 2011;117:1399-408.

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“…Research suggests that relying solely on miRNA detection and can not be used as basis for determining the diagnosis of colorectal cancer, but it can provide a theoretical basis for the incidence of colorectal cancer, provide targets for future therapy (Corte et al, 2012;Giraldez et al, 2013;. This study started from the mutual relationships between DNA methylation and miRNA, aiming to find the new mechanism towards the occurrence of colorectal cancer from the complex gene regulatory networks, thus providing new theoretical and experimental data for the diagnosis and treatment of colorectal cancer (Vire et al, 2006;Kim et al, 2008;Vilkin et al, 2009). The studies had shown that the imbalance of miRNA-34a-5p expression could lead to the occurrence of a variety of tumors in vivo, such as prostate cancer and breast cancer, etc (Guessous et al, 2010;Liu et al, 2011;Vinall et al, 2012), while there was few report about the roles of miRNA-34a-5p in colorectal cancer, so how exactly were the roles of miRNA-34a-5p in colorectal cancer?…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of miRNA-34a in Colorectal Cancer

Kong²,

Cui³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. Materials and Methods: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. Results: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). Conclusions: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.

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T2093 Microsatellite Instability (MSI), Hmlh1 Promoter Hypermethylation and BRAF Mutation Analysis in Sporadic Colorectal Cancers (Crcs) of Different Ethnic Groups in Israel

Cited by 8 publications

References 0 publications

Is BRAF Mutation Associated with Interval Colorectal Cancers?

Is BRAF Mutation Associated with Interval Colorectal Cancers?

Phosphorylated AKT expression is associated with PIK3CA mutation, low stage, and favorable outcome in 717 colorectal cancers

Expression and Clinical Significance of miRNA-34a in Colorectal Cancer

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