Incidence and characteristics of BRAF V600E mutation in colorectal cancer (CRC) with mismatch repair (MMR) protein defect due to loss of MLH1: A prospective evaluation of 104 consecutive patients.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3539-3539
Author(s):  
S. A. Mahesh ◽  
E. Hanna ◽  
M. S. Khan ◽  
P. Ravichandran ◽  
F. Slezak
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Prospective Evaluation

scholarly journals BRAF Mutations as Actionable Targets: A Paradigm Shift in the Management of Colorectal Cancer and Novel Avenues

2021 ◽  
pp. OP.21.00160
Author(s):  
Ibrahim Halil Sahin ◽  
Jim Klostergaard
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Growth Factor Receptor ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Class I ◽  
Molecular Characteristics ◽  
Braf Mutations ◽  
Therapy Choice ◽  
Checkpoint Inhibitor Therapy

BRAF mutations in colorectal cancer have been studied over the past several decades. BRAF V600E mutation, a class I mutation, is the most common oncogenic BRAF alteration in colorectal cancer. Until recently, the BRAF V600E mutation was not among actionable genes for colorectal cancer. However, recent discoveries have revealed therapeutic opportunities. The BRAF with or without MEK inhibition combined with epidermal growth factor receptor–directed therapy was recently found to be an effective therapy choice for patients with advanced-stage BRAF V600–mutant colorectal cancer. However, it is essential to distinguish patients with BRAF V600E–mutant mismatch repair–deficient colorectal cancer from those with mismatch repair–proficient colorectal cancer, as immune checkpoint inhibitor therapy is more appealing in this subset of patients with colorectal cancer. This review article discusses the molecular characteristics of class I, II, and III BRAF mutants and their impact on the clinical behavior of colorectal cancer. We also review the recent progress in the targetability of BRAF mutations in colorectal cancer, which has led to changes in clinical practice and elaborates on innovative therapeutic approaches to enhance the efficacy of BRAF-targeting therapies, to achieve more durable responses.

Systemic Therapy for Colorectal Cancer

2019 ◽  
Author(s):  
Anna M. Varghese
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Targeted Therapies ◽  
Growth Factor Receptor ◽  
Braf V600e ◽  
Ongoing Research ◽  
Medical Oncologists ◽  
Epidermal Growth ◽  
Cytotoxic Therapies

Colorectal cancer remains the second most common cause of cancer-related deaths in this country. Although colorectal cancer is best managed by a multidisciplinary team of surgical, radiation, and medical oncologists, cytotoxic therapy remains the backbone of treatment in the metastatic disease setting. In addition to cytotoxic therapies, vascular-targeted therapies and epidermal growth factor receptor (EGFR)–targeted therapies for selected patients with metastatic colorectal cancer improve outcomes for patients with metastatic colorectal cancer. Growing understanding of various biological subsets of colorectal cancer, including BRAF V600E mutant and mismatch repair–deficient colorectal cancers, is expanding treatment opportunities for patients and is the focus of ongoing research. This review contains 4 tables and 57 references. Key Words: chemotherapy, colorectal cancer, fluoropyrimidines, immunotherapy, metastatic, mismatch repair–deficient colorectal cancer, targeted therapy, topoisomerase inhibitors

scholarly journals BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features

2016 ◽  
Vol 17 (8) ◽  
pp. 840-848 ◽  
Author(s):  
Cristin Roma ◽  
Anna Maria Rachiglio ◽  
Raffaella Pasquale ◽  
Francesca Fenizia ◽  
Alessia Iannaccone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Pathologic Features

Defective mismatch repair proteins and microsatellite instability in young Mexican patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14708-e14708
Author(s):  
Arturo Quintanilla Guzman ◽  
Arturo Luevano Gonzalez ◽  
Augusto Rojas Martinez ◽  
Juan Pablo Flores Gutierrez ◽  
Juan Francisco Gonzalez Guerrero ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Young Patients ◽  
Gene Promoter ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Braf Mutations ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Msi Analysis

e14708 Background: Colorectal carcinoma (CRC) is prevalent malignancy and a third of the cases affect young patients. 15% of CRC have microsatellite instability (MSI) due to disruptions in mismatch repair (MMR) genes, like germline mutations (3%) and hypermethylation of the MLH1 gene promoter associated to the BRAF V600E mutation (12%). The aim of this work was to assess MMR abnormalities in tumors of Mexican CRC patients under 50 years old. Methods: CRC paraffin-embedded tissues of 47 patients with available demographic/clinical data were studied by immunohistochemistry (IHC) for MLH1/MSH2, qPCR with specific probes/sequencing for the BRAF V600E mutation, and conventional PCR (5 markers) for MSI analysis. Results: Female:Male ratio was 0.81:1. Most of the cases were classified as TNM Stage II, were located in the cecum, invaded the serous coat, and showed intestinal-type histology. 20 samples showed alterations in MMR protein expression. MLH1, MSH2, and combined deficiency of both proteins were detected in 17, 4, and 4 tumors, respectively. No BRAF mutations were detected. MSI analysis restricted to the 20 altered IHC samples showed MSI in 10 tumors (3 MSI-low and 7 MSI-high tumors). The four cases with MLH1/MSH2 deficiency, showed MSI-high pattern. Conclusions: We found 42.6% cases with defective MMR expression. No epigenetic abnormalities associated to BRAF V600E mutation were registered. The lack of MSI in ten tumors with deficient MMR may be due to alternate DNA repair mechanisms. Acknowledgments. Work supported by the CHIBCHA Project (European Commission7FP grant #223678).

scholarly journals BRAF V600E mutation and KRAS codon 13 mutations predict poor survival in Chinese colorectal cancer patients

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Chen ◽  
Fang Guo ◽  
Xin Shi ◽  
Lihua Zhang ◽  
Aifeng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Poor Survival ◽  
Colorectal Cancer Patients ◽  
Kras Codon

scholarly journals Clinicopathological Significance of BRAF V600E Mutation in Egyptian Colorectal Cancer Patients

2020 ◽  
Vol 88 (6) ◽  
pp. 991-997
Author(s):  
MONA A. KORA, M.Sc.; NANSY Y. ASAAD, M.D. ◽  
HALA S. EL-REBEY, M.D.; RANIA A. HASSANIN, M.D. ◽  
ALSHIMAA M. ALHANAFY, M.D.
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Clinicopathological Significance ◽  
Colorectal Cancer Patients

scholarly journals Detection of the BRAF V600E Mutation in Colorectal Cancer by NIR Spectroscopy in Conjunction with Counter Propagation Artificial Neural Network

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2238 ◽  
Author(s):  
Xue Zhang ◽  
Yang Yang ◽  
Yalan Wang ◽  
Qi Fan
Keyword(s):  
Neural Network ◽  
Colorectal Cancer ◽  
Artificial Neural Network ◽  
Nir Spectroscopy ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Ann Model ◽  
Wild Type ◽  
Tissue Samples ◽  
Cp Ann

This paper proposes a sensitive, sample preparation-free, rapid, and low-cost method for the detection of the B-rapidly accelerated fibrosarcoma (BRAF) gene mutation involving a substitution of valine to glutamic acid at codon 600 (V600E) in colorectal cancer (CRC) by near-infrared (NIR) spectroscopy in conjunction with counter propagation artificial neural network (CP-ANN). The NIR spectral data from 104 paraffin-embedded CRC tissue samples consisting of an equal number of the BRAF V600E mutant and wild-type ones calibrated and validated the CP-ANN model. As a result, the CP-ANN model had the classification accuracy of calibration (CAC) 98.0%, cross-validation (CACV) 95.0% and validation (CAV) 94.4%. When used to detect the BRAF V600E mutation in CRC, the model showed a diagnostic sensitivity of 100.0%, a diagnostic specificity of 87.5%, and a diagnostic accuracy of 93.8%. Moreover, this method was proven to distinguish the BRAF V600E mutant from the wild type based on intrinsic differences by using a total of 312 CRC tissue samples paraffin-embedded, deparaffinized, and stained. The novel method can be used for the auxiliary diagnosis of the BRAF V600E mutation in CRC. This work can expand the application of NIR spectroscopy in the auxiliary diagnosis of gene mutation in human cancer.

scholarly journals The impact of the Glasgow Prognostic Score on survival in second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation

2019 ◽  
Vol 11 ◽  
pp. 175883591882029 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hiroya Taniguchi ◽  
Keiji Sugiyama ◽  
Toshiki Masuishi ◽  
Kazunori Honda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Colorectal Cancer Patients ◽  
Line Chemotherapy

Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E mutant colorectal cancer is associated with short survival. Recently, clinical trials have been conducted to improve outcomes of second or later lines of chemotherapy. However, there is a paucity of reference data pertaining to outcomes of second-line chemotherapy and prognostic factors that are relevant only to BRAF mutant patients. Patients and methods: We retrospectively reviewed metastatic colorectal cancer patients with BRAF V600E mutation who underwent second-line chemotherapy between January 2007 and March 2017. We evaluated treatment outcomes and performed prognostic analyses. Results: A total of 52 patients were included. The median progression-free survival and overall survival (OS) were 2.5 [95% confidence interval (CI) = 1.91–4.11] and 6.5 (95% CI = 4.30–9.63) months, respectively. Overall response and disease control rates were 7% and 48%, respectively. All the regimens which elicited a partial response included BRAF inhibitors in combination with anti-epidermal growth factor receptor (EGFR) antibodies. Therefore, the overall response was 0% after exclusion of patients treated with study drugs. Multivariate analysis for OS revealed that the Glasgow Prognostic Score (GPS), elevated lactate dehydrogenase, and poor performance status were independent prognostic factors. In particular, survival curves according to the GPS stratified the patients into distinct risk groups. The median OSs in patients with GPS of 0, 1, and 2 were 9.9, 5.0, and 1.9 months, respectively. Conclusions: Outcomes of second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation were extremely poor. GPS may be useful in future clinical trials.

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