"In humans, serrated colorectal cancers are associated with either BRAF or KRAS mutations."
"In agreement with others ( xref - xref ), we found that KRAS mutations were highly associated with lung-only metastases and BRAF mutations with peritoneal and nodal-only metastases."
"Additionally, we showed that KRAS or BRAF mutation could be associated with improved prognosis in MSI-positive colorectal cancers."
"Treatment of KRAS * MEFs with YZ0711 also resulted in decreased RAS bound BRAF, suggesting YZ0711 can disrupt RAS signaling (XREF_FIG)."
"Since mutations in the KRAS and BRAF genes are associated with resistance to therapy with anticancer drugs targeting the EGF receptor pathway, the analysis of KRAS and BRAF mutational status has become an important tool in the clinical management of patients with advanced colorectal cancer."
"The validity of the findings are however strengthened by the expected associations of KRAS and BRAF mutations with clinicopathological factors, e.g. KRAS and BRAF mutations being mutually exclusive [ xref ], the significant associations between BRAF mutation, MSI [ xref , xref , xref ] and mucinous phenotype [ xref , xref ]."
"Similarly, it completely suppressed the effects of exogenous KRAS G12C expression on KRAS-GTP levels, KRAS-BRAF interaction, and ERK signaling ( xref )."
"Importantly, a MEK inhibitor (U0126) had no impact on KRAS G12V −BRAF or KRAS G12V −CRAF interactions (Supplementary Fig. xref , d)."
"BRAF mutations, but not KRAS mutations, were associated with a worse outcome in Chinese CRC patients."
"Recent molecular advances have shown two molecular phenotypes of TSA: one associated with BRAF mutations and the other with KRAS mutations."
"Interestingly, objective response was not associated with the presence of KRAS or BRAF mutation, although the importance of a specific mutational variant was not described."
"We found no evidence for an association of KRAS or BRAF mutation with telomere length."
"In the present study, we examined the associations of specific KRAS and BRAF mutations with clinicopathological and tumour biological characteristics, and survival, in 525 incident cases of colorectal cancer from a prospective population-based cohort study."
"Conversely, two recent studies conclude KRAS and BRAF mutations are associated with inferior survival in Japanese patients with stage I–III disease xref and significantly poorer disease-free survival (DFS) (3-year DFS 79% and 92% in mutant and wild-type respectively; p = 0.006) xref ."
"Indeed, KRAS binds to and activates BRAF, thereby activating MAPK signaling pathways."
"High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations."
"Indeed it's possible that both KRAS and BRAF mutations are associated with a worse biology and a more rapid and aggressive metastatic behavior of CLM, discouraging surgeons to perform surgical re[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"Mutations in KRAS or BRAF are associated with resistance to AKT inhibitors and inhibition of PI3K/AKT/mTOR signaling may lead to activation of the MEK/ERK signaling xref – xref which can confer resistance to PI3K pathway inhibitors xref – xref ."
"Likewise, KRAS and BRAF mutations are inversely associated in CRC, consistent with the fact that both induce similar effects through the same pathway, since the B-Raf protein kinase is activated by membrane-bound Ras."
"The diffuse expression found in 36 of 63 (57.1%) patients was significantly associated with mutation in either KRAS or BRAF , compared with 32.1% of patients with a patchy expression ( P <0.001)."
"To determine whether this complex formation–enhancing effect is a general property of vemurafenib, we set out to test the drug effect on the BRAF interactions with KRAS G12V , NRAS G12V , and HRAS G12V . This time, we analyzed the dose-dependent effect using 100 nM and 1 μM vemurafenib."
"This meta-analysis, including seven studies, which evaluated the survival outcomes (OS, and/or RFS) of patients undergoing hepatic resection of CLM, stratified by KRAS and/or BRAF mutation status, has[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"We separately conducted two-way models of CIMP interaction with BRAF and KRAS , but found no significant interactions in either unadjusted or adjusted models for overall and disease-free survival (data not shown)."
"Typically, LGSC is also associated with KRAS and BRAF mutations that target specific cell signaling pathways [ xref – xref ]."
"KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC."
"It has been
demonstrated that KRAS and BRAF kinases may form their own unique signaling networks in
addition to the shared function in activating MEK signaling xref – xref ."
"KRAS codon 12 and 13 mutations have been inversely associated with BRAF mutation in colorectal cancer
[ xref , xref , xref , xref ]."
"Right-sided tumours have been associated with the presence of KRAS [ xref , xref ] and BRAF [ xref – xref ] mutations."
"In colorectal cancers, unlike KRAS , BRAF mutations are associated with clinocopathological features and play a negative prognostic role."
"Analysis of KRAS binding to B-Raf proto-oncogene, serine/threonine kinase showed that the KRAS(G48A) mutant behaves more like a wild-type than a classical KRAS(G12) mutant."
"High miR-31 expression was associated with BRAF and KRAS mutations and proximal location (P < 0.0001)."
"Together these results demonstrate that oncogenic forms of BRAF and KRAS can activate ERK1/2 but cannot activate ERK5 in HEK293 cells."
"The association of mutations in KRAS and BRAF, as well as MMR status, with clinical outcome by tumor site was found to be consistent with the overall cohort ( xref )."
"Activating mutations in either BRAF or KRAS are associated with serrated polyps in humans xref , xref ."
"However, except for a weak interaction between KRAS and BRAF wild‐type status and benefit from preoperative chemotherapy ( p = 0.02), no statistically significant interaction between mutation status for any of the genes analyzed and benefit from chemotherapy administered in the preoperative or postoperative setting was recorded (Supporting Information Figs."
"R11.1.6 inhibits intrinsic K-Ras activity and interaction with B-Raf."
"The associations between CIMP status and BRAF, KRAS and MSI-H were stronger for females than males (XREF_TABLE, all interaction p < 0.0012)."
"In more specific analyses on MSI-high CRC, regular use of NSAIDs was associated with much stronger risk reduction in the absence of BRAF or KRAS mutations (OR = 0.34, 95% CI = 0.18 to 0.65) but not with KRAS- or BRAF-mutated MSI-high CRC (Pheterogeneity < ."
"Also the role of the KRAS-BRAF interaction (being BRAF an effector of RAS in the RAF and PI3K activated pathways) is far from being understood."
"SPR experiments demonstrated that B-Raf binds to Ki-Ras forming a complex with RACK1."
"We quantitatively assessed this correlation by plotting the potency of inhibitors to induce the BRAF−BRAF kinase domain BRET signal against their potency to stimulate the KRAS G12V −BRAF interaction (Fig. xref and Supplementary Fig. xref , b)."
"Therefore, the aim of our study was to determine whether BRAF or KRAS mutations in sebaceous neoplasms are associated with somatic versus germline mutations, analogous to CRC in LS."
"The most studied are mutations of the KRAS and BRAF genes, which are associated with resistance to epidermal growth factor receptortargeted therapy."
"Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS WT , we also aimed to investigate the KRAS-BRAF interaction."
"KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial."
No evidence text available
"As an alternative and more sensitive measure of ERK5 activity in cells, we used a GAL4 UAS:luciferase reporter system which is driven by the transactivation domain of MEF2D (an ERK5 substrate that is transcriptionally active when phosphorylated) fused to the GAL4 DNA binding domain. xref The ERK5 MEF2D:GAL4 UAS:luciferase reporter system was transfected into HEK293 cells with either wild type MEK5 and the oncogenic forms of KRAS or BRAF or MEK5D for 24h."
"On the basis of previous reports,
we investigated the prognostic associations of KRAS and BRAF mutations in relation to MSI status by pooling[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"On the basis of previous reports, xref , xref , xref , xref , xref , xref we investigated the prognostic associations of KRAS and BRAF mutations in relation to MSI status by pooling data from an extended set of the QUASAR 2 and Australian cohorts, including an additional 676 colorectal cancers from QUASAR 2 and 362 stage II or III colorectal cancers from the Australian cohort (n=1732)."
"One large cohort study which recruited 1110 Chinese CRC patients revealed that mutant KRAS and BRAF were associated with right-sited tumors [ xref ] and it correlated with the poor response to epidermal growth factor receptor (EGFR) inhibition with cetuximab [ xref ]."
"In our work, while we confirmed this finding for V600E mutations, BRAF non-V600E mutations (one D594G, two D594N, one G469E, and one G466E) were associated with KRAS mutations (two G13C, one G13D, o[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"In the Ras pathway, K-Ras binds to and activates B-Raf, thereby activating mitogen activated protein kinase (MAPK) signaling, and oncogenic K-Ras activation enables anchorage independent growth in vitro [XREF_BIBR, XREF_BIBR]."
"It is tempting to suggest that specific KRAS and BRAF mutation interaction may have a role to modulate gene expression profiling in specific tumor types (either MSS, or MSI, or CIN) toward a more aggressive phenotype."
"KRAS or BRAF mutations were not associated with overall survival disadvantages in either African Americans or Caucasians."
"While resistance to Rapalogs has been associated with mutations in FKBP12 or the FKB domain of TOR in yeast [ xref ], in human, it has been mostly associated with KRAS and BRAF mutations [ xref ]."
"In our study, BRAF and KRAS mutations associated with a tendency towards higher proliferation rate ( P =0.091) and with a tendency towards lower tumour necrosis percentage ( P =0.172), while SACs had similar proliferation rate ( P =0.354) but significantly lower tumour necrosis percentage relative to CCs ( P =0.014)."
"In particular, the present case appears to support the hypothesis that the co-occurrence of KRAS and BRAF mutations is associated with more aggressive clinical manifestations."
"KRAS binds to BRAF, and thus both genes are part of the EGFR family signalling cascade."
"Accordingly, recent data suggest that BRAF or KRAS mutation are associated with poor prognosis specifically in patients with MSS cancers ( xref ; xref )."
"More specifically, alteration in RA HSC involved decreased interaction between K-Ras and B-Raf."
"KRAS and BRAF mutations are usually associated with poor prognosis and chemotherapeutic resistance in various solid malignancies ( xref ; xref )."
"Structural studies of RAF proteins have identified the valine at position 600 as a crucial site within the conserved kinase domain, which is required for BRAF to maintain an inactive conformation in the absence of KRAS-BRAF interaction [ xref ]."
"However, anti-EGFR therapy resistance is associated with KRAS or BRAF mutation [ xref , xref ]."
"The case shows, that the concomitant KRAS and BRAF mutations is associated with more severe disease."
"Moreover, the wild type forms of KRAS and BRAF were most common among Asians ( xref )."
"While mutation of KRAS and BRAF was associated with conventional adenoma and SSA, respectively (see above), BRAF and KRAS mutation occurred with similar frequency in both MPs (40% and 50%, respectively) and SAs (33% and 27%, respectively)."
"In comparison to 20q diploid CRC, 20q gain/amplification was associated with wild-type (WT) KRAS (p<0.001) and BRAF (p=0.01), microsatellite stability (MSS) (p<0.001), distal primary tumors (p<0.001), and mutant TP53 (p<0.001), but not stage."
"We also tested whether other significant genetic or clinical status involved in CRC development, such as APC and TP53 mutations, MSI and TNM-Duke's staging, were related with the observed BRAF- or K-ras associated expression profiles."
"To this end we employed HEK293 cells and transiently transfected ERK5 and its upstream activator MEK5 (wt), together with either the active forms of KRAS (KRAS G12V ) or BRAF (BRAF V600E ) or the kinase dead form of BRAF (BRAF D594A ) and KRAS G12V (as they are known to co-operate with CRAF in ERK1/2 signaling xref )."
"KRAS mutation, present in 30%-40% of tumors, does not appear to be an independent negative prognostic factor, in that patients in the control arms of studies of EGFR inhibitors in colorectal cancer demonstrate similar outcomes regardless of KRAS mutational status. xref - xref Interestingly, the V600E mutation in BRAF, another gene in the KRAS signal transduction pathway, is also associated with nonresponse to EGFR-targeted therapy based upon early data. xref - xref Subset analyses from the CAIRO-2, CRYSTAL, and PETACC-3 trials suggest that the BRAF V600E mutation, unlike KRAS mutation, is associated with poor prognosis which may confound interpretation of its predictive value. xref - xref BRAF mutations are present in approximately 5% to 10% of colorectal tumors and appear to be mutually exclusive with KRAS mutations. xref , xref , xref , xref BRAF mutation may be more common in patients with the CpG island methylator phenotype (CIMP), which itself has been associated with a positive prognosis, highlighting the complexity of these molecular pathways. xref "
"The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases."
"K-ras or B-raf mutations are associated with low grade (type I) serous carcinoma."
"Furthermore, MSI and CIN are each associated with specific molecular changes, such as mutations in KRAS and BRAF, that have been associated with prognosis."
"In comparison with 20q diploid colorectal carcinoma, 20q gain/amplification was associated with wild-type KRAS ( P < 0.001) and BRAF ( P = 0.01), microsatellite stability ( P < 0.001), distal primary tumors ( P < 0.001), and mutant TP53 ( P < 0.001), but not stage."
"As an example, sessile serrated polyps can potentially develop more aggressively into colorectal cancer as compared to other colorectal polyps, because of the serrated pathway in tumorigenesis.[ xref ] The serrated pathway is associated with mutations in the BRAF or KRAS oncogenes, and CpG island methylation, which can lead to the silencing of mismatch repair genes (e.g., MLH1 ) and a more rapid progression to malignancy.[ xref ] Therefore, differentiating sessile serrated polyps from other types of polyps is critical for an appropriate surveillance.[ xref ] Histopathological characterization is the only reliable existing method for diagnosing sessile serrated polyps because other screening methods designed to detect premalignant lesions (such as fecal blood, fecal DNA, or virtual colonoscopy) are not well suited for differentiating sessile serrated polyps from other polyps.[ xref ] However, differentiation between sessile serrated polyps and innocuous hyperplastic polyps is a challenging task for pathologists.[ xref xref xref xref ] This is because sessile serrated polyps, such as hyperplastic polyps, often lack the dysplastic nuclear changes that characterize conventional adenomatous polyps, and their histopathological diagnosis is entirely based on morphological features, such as serration, dilatation, and branching."
"In Chinese CRC patients, Shen et al found that gender was the only factor that showed an obvious relationship with KRAS mutations (female 44.7% vs male 28.2%, P = 0.037) xref ; Liou et al reported more frequent KRAS mutations in females and in non-smokers, and KRAS and BRAF mutations were significantly associated with the proximal location of cancer xref ."
"Mutations in KRAS and BRAF have been associated with a lack of benefit from anti-EGFR monoclonal antibodies in metastatic colorectal cancer."
"In the NSHDS cohort mutated KRAS and BRAF tumours were associated with right colon location, most distinct for BRAF (NSHDS; P <0.001)."
"We investigated the prognostic associations of KRAS and BRAF mutations in relation to MSI status by pooling data from the QUASAR 2 gene panel, the Australian validation set, and additional QUASAR [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
"Fourth, MC was associated with higher BRAF V600E mutation rate and lower KRAS mutation rate compared to PDA/UDA and conventional AdCa."
"BRAF and KRAS activating mutations are associated with development of serrated lesions in humans xref , xref ."
"Ogino and colleagues examined the interaction between T cell infiltration and KRAS, BRAF, and PIK3CA mutation status and found no significant associations with KRAS mutation, XREF_BIBR but this study was limited to the density of CD3 +, CD8 +, CD45RO +, and FoxP3 + cells."
"Several research groups have provided evidence that two proto-oncogenes, KRAS and BRAF , are associated with resistance to chemotherapy and poor prognosis [ xref , xref , xref , xref , xref , xref , xref , xref , xref , xref ], as confirmed by the survival analysis of the BRAF mutated CRCLM included in the TCGA cohort ( xref B)."
"MSI-H has been associated with lower incidence of lymphatic metastasis and BRAF and KRAS mutations are associated with distant metastasis.[ xref ] Our patient was treated with FOLFIRI and he has shown good response to therapy."
"The results from the CRYSTAL and OPUS studies indicate that the benefit from the addition of cetuximab to first-line chemotherapy is restricted to patients with the wild-type KRAS gene, with the best outcomes observed among those with unmutated forms of both the KRAS and BRAF genes."
"An ongoing phase II trial (GOG 0239) of AZD6244, a MEK inhibitor, should determine whether there is clinical benefit in targeting MEK pathway for patients with LGSC and whether the response is associated with mutations of BRAF and KRAS ."
"According to the molecular features of common pancreatic ductal neoplasms, IPMNs are frequently associated with mutations in KRAS and BRAF [ xref ]; however, mutations in the genes involved in the PI3K pathway, including PIK3CA, PTEN, and AKT1, are very rare in common pancreatic ductal neoplasms [ xref , xref ]."
"In contrast to the findings of this study, several reports have suggested the association of KRAS or BRAF mutations with poorer outcome compared with wild-type KRAS or BRAF in a variety of malignancies ( xref ; xref ; xref )."
"We measure the signalling response using a bead-based ELISA, and use a panel of three cell lines, and isogenic cell lines that express mutant forms of the oncogenes KRAS and BRAF to interrogate the effects of the MEK and RAF inhibitors on signalling."
"The finding of no interaction (except for a weak association between KRAS and BRAF wild-type status and benefit from preoperative therapy) between gene mutation status and mutation heterogeneity on the one hand and benefit from chemotherapy on the other hand further supports a prognostic role of these mutations, suggesting mechanisms related to tumor cell growth, invasion, metastatic propensity and others and not resistance to chemotherapy to explain our observations."
"BRAF or KRAS mutations were independently associated with adverse outcome."
"In addition, IQGAP1 expression increased the interaction between K-Ras and B-Raf, and knock-down of IQGAP1 decreased the interaction between K-Ras and B-Raf ( Fig. 4 )."
"In the 116 patients with KRAS wild-type tumors, BRAF mutations ( n = 5) were weakly associated with a lack of response ( P = 0.063) but strongly associated with a shorter PFS ( P < 0.001) and OS ( P < 0.001)."
"In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance ( P = 0.052 and 0.094, respectively)."
"Interestingly, BRAF mutations, which are predominantly mutually exclusive of mutant KRAS , have also been associated with resistance to anti-EGFR treatment in colorectal cancer [ xref , xref ]."
"Previous studies have reported a close association of extensive KRAS and BRAF mutations in pancreatic cancers, hepatocellular carcinomas, colorectal cancers and malignant melanomas [3,4] ."
"MKP-2 was also found to be highly expressed in intestinal epithelial cells expressing oncogenic forms of KRAS and BRAF, and in KRAS and BRAF mutant CRC cells, with corresponding nuclear ERK inhibition ( xref )."
"Interestingly, the most significant correlation (p = 4.63E-07) was that of the BRAF-KRAS interaction to PLX4720, a compound that targets BRAF."
"For example, K-Ras and BRAF mutations have been associated with some cases of CAC as well."
"It was found that adding cetuximab to chemotherapy improved outcomes for all patients with normal forms of KRAS, regardless of BRAF status, but that those with normal forms of both the KRAS and BRAF genes benefited most."
"KRAS and BRAF mutations were associated with CAD/TSA and HPP/SSA, respectively."
"Gnomonic research has found that PTC and MTC are associated with point mutations in K-RAS and BRAF genes, and that FTC harbors PAX8-PPAR gamma fusions genes xref xref xref ."
"Narita et al. reported that KRAS and BRAF mutations in the tumour tissue are associated with elevated CA 19–9 levels (25)."
"Since the discovery of mutated forms of KRAS and BRAF as mutually exclusive drivers of colorectal carcinogenesis, much progress has been made in understanding their common and individual effects."
"Accumulation of specific genetic and epigenetic events results in disease progression along three distinct clinico-pathologic pathways involving DNA methylation, microsatellite instability, and epigenetic-genetic interactions affecting mutations of KRAS or BRAF oncogenes and the p53 tumor suppressor genes xref , xref ."
"KRAS mutation, but not BRAF V600E mutation, is significantly associated with invasive implants of serous borderline tumor."
"Indeed, the use of isogenic colorectal cancer cell lines that express either the mutant or the wild-type form of K-RAS or B-RAF shows that the enzymes of the non-oxidative branch of the PPP (ribose-5-phosphate isomerase and TKT) are upregulated in the K-RAS-mutant cell lines ( xref )."
"Response to neoadjuvant chemotherapy has been related to improved survival, xref whereas KRAS and BRAF mutations have been associated with more aggressive disease and a poor prognosis. xref , xref , xref , xref While liver resection for metastatic CRC (mCRC) has become routine practice, xref the fact that the majority of patients undergoing surgery subsequently relapse xref underlines the need for better predictive markers guiding treatment decisions."
"Genetic alterations can contribute to metastatic phenotypes, as we show in the MDA-MB-231 triple-negative breast carcinoma model and as the presence of KRAS or BRAF mutations have been associated with increased metastasis in colorectal cancer ( xref - xref )."
"Type I tumors are associated with mutations in BRAF and KRAS oncogenes in serous and mucinous tumors, and PTEN in endometroid tumors, all of which are not characteristic of HGSOC tumors which predominantly (~50%–80%) have p53 mutations xref ."
"With regards to availability of other potential prognostic biomarkers in CRC, the association of BRAF and KRAS mutations, CIMP (CpG island methylator phenotype) and MSI (microsatellite instability) status have been studied extensively."
"More specifically, alteration in RA HSC involved decreased interaction between K-Ras and B-Raf."
"Evidence has also suggested that mutations in KRAS proto-oncogene GTPase ( KRAS ) and B-Raf proto-oncogene serine/threonine kinase ( BRAF ) are associated with a worse patient prognosis in CRC ( xref )."
"We show that mutations to either KRAS or BRAF are associated with the development of early hyperplasia within the distal colon."
"Whereas mice with inactivating mutations in APC rapidly develop tubular adenomas, BRAF or KRAS mutations that are associated with serrated polyps are alone insufficient to provoke intestinal tumorigenesis. xref , xref After a brief period of hyperproliferation, crypt cells undergo growth arrest due to metabolic and replicative stress, a process termed oncogene-induced senescence (OIS)."
"We also found that overexpression or knock-down of IQGAP1 affected the interaction between K-Ras and B-Raf, and IQGAP1 overexpression increased ERK1/2 phosphorylation in K-Ras dependent manner in PANC1 cells."
microsatellite stability and mutations in KRAS or BRAF were
associated with decreased survival times, compared to tumors with
microsatellite stability and no mutations."
"Finally, the presence of either KRAS or BRAF mutations were associated with a down-regulation of a set of genes involved in the cell cycle and telomerase pathway, suggesting that OIS programs may have been activated."
"Non-mutated forms of BRAF ( v-raf murine sarcoma viral oncogene homolog B1) and KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ) genes are required for response to tyrosine kinase inhibitors (TKI).( xref )Immunohistochemistry studies with EGFR showed that patients with high expression are more likely to respond to these drugs than those with reduced expression.( xref )"
"A recent study revealed that both BRAF and KRAS mutations are associated with poorer survival in MSI CRC patients compared to those with wild-type BRAF and KRAS genes [ xref ]."
"This is consistent with the expression of activated forms of KRAS and BRAF in this cell line ( xref )."
"KRAS and BRAF mutations were significantly associated with diploid chromosome 20q (p<0.0001 and p=0.01 for KRAS and BRAF , respectively) in the MSK-IMPACT data."
"In secondary transplantations, the three KMT2A-MLLT3 leukemias with Braf V637E , Kras G12D , or Ptpn11 S506W were associated with accelerated disease (Fig. xref )."
"In order to investigate if the increase in cell viability associated to K-Ras and B-Raf mutation after the treatment was mediated by p73 , we analyzed the apoptotic TAp73 isoforms."
"These results suggested that the BRAF and KRAS codon 13 mutations were associated with a right-sided tumour location."
"Results from other clinical trials have also indicated that the benefit from the addition of cetuximab to first-line chemotherapy seems to be restricted to patients with the wild-type KRAS gene; with the best outcomes being observed in those with unmutated forms of both the KRAS and BRAF genes [ xref - xref ]."
"KRAS and BRAF mutations were significantly associated with the proximal location of cancer (p = 0.017 and 0.001, respectively)."
"More specifically, Zeppernick described some specific morphological features in 71atypical proliferative serous tumors (APSTs) and 18low grade serous carcinomas (LGSCs) and therefore their association with KRAS and BRAF mutations ."
"While the presence of KRAS or BRAF mutation in colorectal cancer is associated with resistance to cetuximab ( xref , xref ), the EGFR characteristics that correlate with colon tumor sensitivity to cetuximab are less well defined."
"In patients with metastatic KRas wild type tumors, BRAF mutations have been associated with shorter progression-free and shorter overall survival [ xref ]."
"This mutation has a minimal impact on MAPK signaling in vitro and has been associated with good response to EGFR-directed therapy and a favorable prognosis in metastatic CRC patients. xref , xref Several individuals with multiple polyps had both serrated and adenomatous polyps associated with BRAF and KRAS mutation, respectively."
"An engineered protein antagonist of K-Ras and B-Raf interaction."
"To optimise the selection of patients who are more likely to benefit from anti-EGFR we investigated in a cohort of patients treated with the combination of cetuximab and irinotecan and bearing KRAS codons 12 and 13 wild-type tumours, the association of KRAS codons 61 and 146 mutations and BRAF V600E mutation with clinical outcomes."
"KRAS mutations were associated with right colon cancers ( P =5.2×10 −5 ) and BRAF mutations with right ( P =7.2×10 −5 ) and transverse colon ( P =9.8×10 −6 ) cancers."
"In a Japanese study by Kadowaki et al, KRAS and BRAF mutations were associated with a shorter survival, xref whereas another Japanese study revealed that the prognostic impact of KRAS mutations on recurrence-free survival was limited in patients with stage II CRC, and KRAS mutations were not associated with OS. xref Conversely, our analysis showed that the KRAS status affects OS and DFS in patients with CRC: KRAS mutations were associated with a shorter OS and DFS compared with wild-type KRAS ."
"Low-grade serous ovarian carcinoma is frequently associated with mutations in BRAF and KRAS , demonstrates mild to moderate nuclear atypia, and often expresses higher levels of estrogen receptors, progesterone receptors, and E-cadherin [ xref ]."
"Clinicopathological and molecular associations of KRAS and BRAF V600E mutations."
"One study examined a mixed population of sixty-nine ICC and ECC cases and mutations in KRAS and BRAF were not associated with differences in prognosis [ xref ]."
"Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma."
"Its direct association with the oncogenic drivers Braf and K-ras points to a contribution of the loop components to murine serrated route tumorigenesis."
"In contrast, the oncogenic forms of KRAS and BRAF did not induce phosphorylation of ERK5."
"However, mutations in KRAS and BRAF genes have been associated with primary resistance to anti-EGFR monoclonal antibodies in CRC and targeted EGFR therapy [ xref ]."
"In the colon, BRAF and KRAS mutations are associated with microsatellite instability and COAD-CIMP [ xref ]."
"However, except for a weak interaction between KRAS and BRAF wild-type status and benefit from preoperative chemotherapy (p = 0.02), no statistically significant interaction between mutation status for any of the genes analyzed and benefit from chemotherapy administered in the preoperative or postoperative setting was recorded (Supporting Information Figs."
"Since primary colonic epithelial cells were not readily available, we screened for colorectal cancer cell lines that do not have substantial DNA methylation at CIMP-defining loci and carry wild-type forms of both BRAF and KRAS ."
"In 3D cultures, Caco‑2 cells transfected with mutated KRAS or BRAF formed multicellular structures analogous to anoikis‑resistant subpopulations in actual carcinomas, and serve as an in vitro model for anoikis resistance."
"As KRAS and BRAF mutations are associated with poor response to anti-EGFR therapy in some cancers, it has been suggested that screening for KRAS and BRAF mutations in RCC may be a promising strategy to identify patients who might respond to EGFR-targeted therapy."
"Of the 19 drugs that had at least one known target, only AZD6244 had its associated proteins and PFRs enriched with its targets, as mutations in two of the five genes known to code for proteins interacting directly with the drug, BRAF and KRAS, are also associated with differential activity for this drug (p<0.005)."
"In line with this study, KRAS or BRAF mutations may be associated with shorter overall survival in patients with MSS but not in those with MSI tumors [ xref ]."
"In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = ."
"Also, KRAS or BRAF mutations were not associated with MMR status."
"In this pooled analysis of metastatic colorectal cancer patients, mutations in KRAS, and BRAF were associated with inferior progression-free and overall survival compared with patients with non-mutated tumors."
"We tested the hypothesis that the association of KRAS and BRAF V600E mutations with clinical outcome depends on the anatomic site of the primary tumor."
"In the univariate analysis, KRAS and BRAF mutations were not associated with survival."