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https://www.readbyqxmd.com/read/29148538/molecular-testing-for-braf-mutations-to-inform-melanoma-treatment-decisions-a-move-toward-precision-medicine
#1
Liang Cheng, Antonio Lopez-Beltran, Francesco Massari, Gregory T MacLennan, Rodolfo Montironi
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29145034/molecular-insight-into-mutation-induced-conformational-change-in-metastasic-bowel-cancer-braf-kinase-domain-and-its-implications-for-selective-inhibitor-design
#2
Kai Zhao, Xin Zhou, Ming Ding
Oncogenic BRAF V600E mutation confers constitutive activation for the kinase and is closely related to the pathogenesis of metastasic bowel cancer (MBC). Here, the V600E-induced conformational change in MBC BRAF kinase domain is characterized systematically at structural, energetic and dynamic levels. The mutation is observed to cause a conformational conversion of the kinase's activation loop from DFG-out to DFG-in, thus activating the kinase. Electrostatic force is primarily responsible for the conformational conversion and stabilization of DFG-in associated with the mutation...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29144823/the-relationship-of-braf-v600e-mutation-status-to-fdg-pet-ct-avidity-in-thyroid-cancer-a-review-and-meta-analysis
#3
Prasanna Santhanam, Rodhan Khthir, Lilja B Solnes, Paul W Ladenson
OBJECTIVES: Papillary thyroid cancers harboring BRAF (V600E) gene mutation have been shown to exhibit aggressive tumor behaviors and higher risks of recurrence and disease-specific death. In this systematic review and meta-analysis, we examine and report published evidence related to the accuracy of FDG-PET-CT in detection of residual disease in patients' with BRAF (V600E) mutated thyroid cancer. METHODS: We extracted data from PUBMED/MEDLINE and EMBASE from January, 1995 to March, 2017...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142786/extraordinary-clinical-benefit-to-sequential-treatment-with-targeted-therapy-and-immunotherapy-of-a-braf-v600e-and-pd-l1-positive-metastatic-lung-adenocarcinoma
#4
Shuyu D Li, Annia Martial, Alexa B Schrock, Jane J Liu
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29141672/a-novel-git2-braf-fusion-in-pilocytic-astrocytoma
#5
Jeffrey Helgager, Hart G Lidov, Navin R Mahadevan, Mark W Kieran, Keith L Ligon, Sanda Alexandrescu
BACKGROUND: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely. CASE PRESENTATION: We present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures...
November 15, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29140771/braf-v600e-status-alone-is-not-sufficient-as-a-prognostic-biomarker-in-pediatric-low-grade-glioma
#6
David T W Jones, Olaf Witt, Stefan M Pfister
No abstract text is available yet for this article.
November 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29138945/glioblastoma-in-neurofibromatosis-1-patients-without-idh1-braf-v600e-and-tert-promoter-mutations
#7
Ichiyo Shibahara, Yukihiko Sonoda, Hiroyoshi Suzuki, Akifumi Mayama, Masayuki Kanamori, Ryuta Saito, Yasuhiro Suzuki, Shoji Mashiyama, Hiroshi Uenohara, Mika Watanabe, Toshihiro Kumabe, Teiji Tominaga
Pilocytic astrocytomas and low-grade gliomas are more common compared with glioblastomas in patients with neurofibromatosis 1 (NF1). A recent genome-wide analysis has shown frequent NF1 gene alterations in the mesenchymal subtype of a glioblastoma; however, little is known about clinicopathological features of glioblastomas in NF1 patients (NF1 glioblastomas). We analyzed four NF1 glioblastomas. Radiographical and intraoperative findings showed well-circumscribed tumors from surrounding brain. Pathological analysis presented a paucity of processes with an eosinophilic cytoplasm, bizarre nuclei, xanthomatous-like appearance, multinucleated giant cells, and histiocytoid appearance...
November 14, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/29137417/inhibition-of-retinoic-acid-receptor-%C3%AE-signaling-confers-glycolytic-dependence-and-sensitization-to-dichloroacetate-in-melanoma-cells
#8
Cecilie Abildgaard, Christina Dahl, Ahmad Abdul-Al, Annette Christensen, Per Guldberg
Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134959/targeting-ret-driven-cancers-lessons-from-evolving-preclinical-and-clinical-landscapes
#9
REVIEW
Alexander Drilon, Zishuo I Hu, Gillianne G Y Lai, Daniel S W Tan
The gene encoding the receptor-tyrosine kinase RET was first discovered more than three decades ago, and activating RET rearrangements and mutations have since been identified as actionable drivers of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers. Nevertheless, response rates to RET-directed therapy are modest compared with those achieved using targeted therapies matched to other oncogenic drivers of solid tumours, such as sensitizing EGFR or BRAF(V600E) mutations, or ALK or ROS1 rearrangements...
November 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29133617/response-and-resistance-to-paradox-breaking-braf-inhibitor-in-melanomas-in-vivo-and-ex-vivo
#10
Edward J Hartsough, Curtis H Kugel, Michael J Vido, Adam C Berger, Timothy J Purwin, Allison Goldberg, Michael A Davies, Matthew J Schiewer, Karen E Knudsen, Gideon Bollag, Andrew E Aplin
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox breaking RAF inhibitor (PLX8394) has been designed. Here we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29132392/false-negative-braf-v600e-mutation-results-on-fine-needle-aspiration-cytology-of-papillary-thyroid-carcinoma
#11
Se Hyun Paek, Byung Seup Kim, Kyung Ho Kang, Hee Sung Kim
BACKGROUND: The BRAF V600E mutation is highly specific for papillary thyroid carcinoma (PTC). A test for this mutation can increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), but a considerably high false-negative rate for the BRAF V600E mutation on FNAC has been reported. In this study, we investigated the risk factors associated with false-negative BRAF V600E mutation results on FNAC. METHODS: BRAF V600E mutation results of 221 PTC nodules between December 2011 and June 2013 were retrospectively reviewed...
November 13, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29128931/universal-determination-of-microsatellite-instability-using-bat26-as-a-single-marker-in-an-argentine-colorectal-cancer-cohort
#12
María Laura González, Natalia Causada-Calo, Juan Pablo Santino, Mev Dominguez-Valentin, Fabiana Alejandra Ferro, Inés Sammartino, Pablo Germán Kalfayan, Maria Alicia Verzura, Tamara Alejandra Piñero, Andrea Romina Cajal, Walter Pavicic, Carlos Vaccaro
Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included...
November 11, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29128185/correct-extent-of-thyroidectomy-is-poorly-predicted-preoperatively-by-the-guidelines-of-the-american-thyroid-association-for-low-and-intermediate-risk-thyroid-cancers
#13
Mashaal Dhir, Kelly L McCoy, N Paul Ohori, Cameron D Adkisson, Shane O LeBeau, Sally E Carty, Linwah Yip
BACKGROUND: Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines. METHODS: We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy...
November 8, 2017: Surgery
https://www.readbyqxmd.com/read/29127628/immunohistochemistry-with-anti-braf-v600e-ve1-mouse-monoclonal-antibody-is-a-sensitive-method-for-detection-of-the-braf-v600e-mutation-in-colon-cancer-evaluation-of-120-cases-with-and-without-kras-mutation-and-literature-review
#14
Katerina Dvorak, Amanda Higgins, John Palting, Michael Cohen, Patrick Brunhoeber
The major aim of this study was to evaluate the performance of anti-BRAF V600E (VE1) antibody in colorectal tumors with and without KRAS mutation. KRAS and BRAF are two major oncogenic drivers of colorectal cancer (CRC) that have been frequently described as mutually exclusive, thus the BRAF V600E mutation is not expected to be present in the cases with KRAS mutation. In addition, a review of 25 studies comparing immunohistochemistry (IHC) using the anti-BRAF V600E (VE1) antibody with BRAF V600E molecular testing in 4041 patient samples was included...
November 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29127087/dabrafenib-plus-trametinib-is-active-in-braf-v600e-anaplastic-thyroid-cancer
#15
(no author information available yet)
Dual BRAF/MEK inhibition achieves responses in 69% of BRAFV(600E) anaplastic thyroid cancers (ATC).
November 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29120401/does-locoregional-chemotherapy-still-matter-in-the-treatment-of-advanced-pelvic-melanoma
#16
Stefano Guadagni, Giammaria Fiorentini, Marco Clementi, Giancarlo Palumbo, Paola Palumbo, Alessandro Chiominto, Stefano Baldoni, Francesco Masedu, Marco Valenti, Ambra Di Tommaso, Bianca Fabi, Camillo Aliberti, Donatella Sarti, Veronica Guadagni, Cristina Pellegrini
Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision...
November 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29119584/concordance-in-braf-v600e%C3%A2-status-over-time-in-malignant-melanoma-and-corresponding-metastases
#17
Line Bjerrehave Nielsen, Nina Dabrosin, Karen Sloth, Marie Louise Bønnelykke-Behrndtz, Torben Steiniche, Johanne Lade-Keller
AIMS: The present study analysed the usability of an immunohistochemical (IHC) analysis compared to a frequently used mutation detection analysis and examined the extent of intra- and inter-tumour heterogeneity of BRAF V600E in primary tumours and their corresponding metastases. In the development of inter-tumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated. METHODS: In total, 227 samples from 224 melanoma patients were analysed using both the Cobas(®) 4800 BRAF V600 Mutation test and IHC anti-BRAF V600E staining...
November 8, 2017: Histopathology
https://www.readbyqxmd.com/read/29118233/hairy-cell-leukemia-version-2-2018-nccn-clinical-practice-guidelines-in-oncology
#18
William G Wierda, John C Byrd, Jeremy S Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E Coutre, Randall S Davis, Christopher D Fletcher, Brian Hill, Brad S Kahl, Manali Kamdar, Lawrence D Kaplan, Nadia Khan, Thomas J Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D Zelenetz, Mary A Dwyer, Hema Sundar
Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29117154/brafv600e-and-ret-ptc-promote-proliferation-and-migration-of-papillary-thyroid-carcinoma-cells-in-vitro-by-regulating-nuclear-factor-%C3%AE%C2%BAb
#19
Dehua Zhou, Zhou Li, Xuefeng Bai
BACKGROUND Papillary thyroid carcinoma (PTC) is associated with mutations of BRAFV600E and RET/PTC and high levels of expression of nuclear factor-κB (NF-κB). However, few studies have focused on the association between NF-κB expression and mutations in BRAFV600E and RET/PTC, especially regarding PTC cell proliferation and migration. The aim of this in vitro study was to investigate the effect of BRAFV600E or RET/PTC on NF-κB expression, cell proliferation and cell migration in four established PTC cell lines...
November 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29110361/hairy-cell-leukemia-2018-update-on-diagnosis-risk-stratification-and-treatment
#20
Xavier Troussard, Edouard Cornet
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation...
December 2017: American Journal of Hematology
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