<i><scp>BRAF</scp></i> mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta‐analysis

Clancy, Cillian; Burke, John P.; Kalady, Matthew F.; Coffey, J. Calvin

doi:10.1111/codi.12427

Cited by 108 publications

(76 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bmutant patients treated with antiBEGFR agents in COIN and PICCOLO have been previously reported, [9,18] Figure 5). These marked differences were independent of firstBline treatment received ( When other prognostic factors were tested in a combined multivariate model, a significant negative effect on PBPS was seen after firstBline chemotherapy for peritoneal metastases and dMMR status (peritoneal metastases HR=1.39, p<0.0001; dMMR HR=1.38, p=0.025).…”

Section: Outcomes Ofmentioning

confidence: 85%

“…[7,8] Importantly previous publications have not performed careful multivariate analysis. This is critical as Bmutant aCRC is associated with clinicopathological features which are themselves negative prognostic factors, [9] including defective mismatch repair (dMMR) status [4,10] , right sided primary tumour location (PTL) [11] and a high incidence of peritoneal metastases. [12] The observed poor outcomes may instead be driven by such factors so it is essential to prospectively factor this into analyses of outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

View full text Add to dashboard Cite

Section: Outcomes Ofmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

et al. 2017

View full text Add to dashboard Cite

“…More than 20 reported trials did not show any prognostic significance, but some have the established negative prognostic value of KRAS mutations on the progression free survival (6,8,9), overall survival (6, 9) or early recurrence after liver surgery for metastases (34). BRAF mutations are not only associated with a more aggressive tumour phenotype, but are also found to be an independent negative prognostic marker for the overall survival (10,11,35).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies revealed KRAS as an independent predictor of relapse and death (6)(7)(8)(9). BRAF mutation was associated with a distinct tumour phenotype and more aggressive disease (10,11).…”

Section: Introductionmentioning

confidence: 99%

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

Baltruskeviciene¹,

Mickys²,

Žvirblis³

et al. 2016

AML

View full text Add to dashboard Cite

Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance.Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed.Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19-9 level and KRAS mutation was detected (mean CA 19-9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS.Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19-9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information.

show abstract

“…The most common mutation, V600E, renders the kinase constitutively active and occurs in 11% of colorectal carcinoma (3). BRAF mutations are implicated as early "signature events" in the so-called serrated pathway describing the progression from serrated adenoma to colorectal carcinomas (2,4).…”

Section: Introductionmentioning

confidence: 99%

B-Raf Inhibitors Induce Epithelial Differentiation inBRAF-Mutant Colorectal Cancer Cells

et al. 2015

View full text Add to dashboard Cite

BRAF mutations are associated with aggressive, less-differentiated and therapy-resistant colorectal carcinoma. However, the underlying mechanisms for these correlations remain unknown. To understand how oncogenic B-Raf contributes to carcinogenesis, in particular to aspects other than cellular proliferation and survival, we generated three isogenic human colorectal carcinoma cell line models in which we can dynamically modulate the expression of the B-Raf V600E oncoprotein. Doxycyclin-inducible knockdown of endogenous B-Raf V600E decreases cellular motility and invasion in conventional and three-dimensional (3D) culture, whereas it promotes cell-cell contacts and induces various hallmarks of differentiated epithelia. Importantly, all these effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametinib). Surprisingly, loss of B-Raf V600E in HT29 xenografts does not only stall tumor growth, but also induces glandular structures with marked expression of CDX2, a tumor-suppressor and master transcription factor of intestinal differentiation. By performing the first transcriptome profiles of PLX4720-treated 3D cultures of HT29 and Colo-205 cells, we identify several upregulated genes linked to epithelial differentiation and effector functions, such as claudin-1, a Cdx-2 target gene encoding a critical tight junction component. Thereby, we provide a mechanism for the clinically observed correlation between mutant BRAF and the loss of Cdx-2 and claudin-1. PLX4720 also suppressed several metastasis-associated transcripts that have not been implicated as targets, effectors or potential biomarkers of oncogenic B-Raf signaling so far. Together, we identify a novel facet of clinically applied B-Raf or MEK inhibitors by showing that they promote cellular adhesion and differentiation of colorectal carcinoma cells.

show abstract

BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta‐analysis

Cited by 108 publications

References 33 publications

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

Investigating the poor outcomes ofBRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

B-Raf Inhibitors Induce Epithelial Differentiation inBRAF-Mutant Colorectal Cancer Cells

Contact Info

Product

Resources

About