Cell-SELEX-based selection of ssDNA aptamers for specific targeting BRAF V600E-mutated melanoma

The Analyst ◽  
2021 ◽  
Author(s):  
Wanming Li ◽  
Tao Bing ◽  
Rui Wang ◽  
Sihan Jin ◽  
Dihua Shangguan ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Malignant Melanoma ◽  
Braf V600e ◽  
Braf Mutations ◽  
Specific Targeting ◽  
Aggressive Form ◽  
Selection Of

Malignant melanoma is regarded as the most aggressive form of skin cancer, and is responsible for most death caused by skin cancer. BRAF mutations occur in approximately 40-50% of melanomas,...

Natural Compounds in the Chemoprevention of Malignant Melanoma

2018 ◽  
Vol 18 (5) ◽  
pp. 631-644 ◽  
Author(s):  
Corina Danciu ◽  
Codruta Soica ◽  
Diana Antal ◽  
Ersilia Alexa ◽  
Ioana Z. Pavel ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Skin Cancer ◽  
Malignant Melanoma ◽  
Treatment Options ◽  
Surgical Excision ◽  
Natural Compounds ◽  
Animal Body ◽  
Chemical Structures ◽  
Biochemical Pathways ◽  
Aggressive Form

Malignant melanoma is a very aggressive form of skin cancer, with increasing rates every year, with an etiology that derives from the transformation and uncontrolled growth of melanocytes. There are several treatment options which can be used as unique treatment or combined, depending upon the stage of melanoma including surgical excision, chemotherapy, immunotherapy, targeted therapy. Plant Kingdom displays an unequalled potential for the synthesis of highly diversified chemical structures. Although natural compounds are synthesized in order to help the plant to interact with the environment, a large number of phytochemicals act as drugs within the human or animal body by activating various biochemical pathways. The study aims to review another approach in the management of this highly aggressive form of skin cancer, namely the effect of natural compounds in the chemoprevention of malignant melanoma.

scholarly journals Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression

2011 ◽  
Vol 104 (3) ◽  
pp. 464-468 ◽  
Author(s):  
J Lin ◽  
Y Goto ◽  
H Murata ◽  
K Sakaizawa ◽  
A Uchiyama ◽  
...  
Keyword(s):  
Primary Melanoma ◽  
Braf Mutations ◽  
Selection Of

scholarly journals High prevalence of somatic MAP2K1 mutations in BRAF V600E–negative Langerhans cell histiocytosis

Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1655-1658 ◽  
Author(s):  
Noah A. Brown ◽  
Larissa V. Furtado ◽  
Bryan L. Betz ◽  
Mark J. Kiel ◽  
Helmut C. Weigelin ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Genome Sequencing ◽  
High Frequency ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Braf Mutations ◽  
Key Points ◽  
High Prevalence

Key Points Targeted genome sequencing reveals high-frequency somatic MAP2K1 mutations in Langerhans cell histiocytosis. MAP2K1 mutations are mutually exclusive with BRAF mutations and may have implications for the use of BRAF and MEK targeted therapy.

scholarly journals Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Bilgen Gençler ◽  
Müzeyyen Gönül
Keyword(s):  
Side Effects ◽  
Metastatic Melanoma ◽  
Mapk Pathway ◽  
Case Reports ◽  
Mitogen Activated Protein Kinase ◽  
Braf V600e ◽  
Braf Inhibitors ◽  
Braf Mutations ◽  
Cutaneous Side Effects ◽  
Downstream Signaling

The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40–60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA). Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.

SCRUM-Japan genesis virtual sequencing (VSQ) project: A novel algorithm combining deep learning (DL) with pathological diagnostics to enable the prediction of BRAF mutations and microsatellite instability (MSI) in advanced colorectal cancer (CRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 112-112
Author(s):  
Satoshi Fujii ◽  
Daisuke Kotani ◽  
Masahiro Hattori ◽  
Nishihara Masato ◽  
Toshihide Shikanai ◽  
...  
Keyword(s):  
Prediction Models ◽  
High Accuracy ◽  
Cancer Genome ◽  
Morphological Features ◽  
Braf V600e ◽  
Next Generation ◽  
Braf Mutations ◽  
Genetic Abnormalities ◽  
Image Prediction ◽  
Novel Algorithm

112 Background: Numerous genetic and epigenetic abnormalities may lead to various morphologies of cancer. However, exactly which gene abnormality causes which morphology is unknown. The VSQ Project aims at investigating a novel algorithm by synergistically fusing DL technology and pathological diagnostics for the prediction of cancer genome abnormalities. This was achieved by elucidating the association between the morphological findings and genetic abnormalities, including BRAF V600E mutations and MSI status directly linked to the therapeutic strategies for advanced CRC patients (pts). Methods: Clinicopathological-genomic integrated DB derived from SCRUM-Japan GI-SCREEN, a nation-wide cancer genome screening project including CRC, were used. A total of 1,657 images of thin sections (one representative image per pt) cut from formalin-fixed and paraffin-embedded (FFPE) tissue specimens from primary or metastatic tumors with genetic abnormalities confirmed by next-generation sequencing (NGS) were investigated; 1,234 and 423 images (one per pt) were used for training and validation cohorts, respectively. First, we developed image-prediction models based on the morphological features precisely annotated by the single central pathologist, and then constructed the DL algorithms (gene-prediction models) that enabled the prediction of gene abnormalities by using images filtered by the image-prediction models. Results: We achieved high accuracy of AUC > 0.90 for 12 features among the 33 morphological features analyzed. Next, we created several DL algorithms that enabled the prediction of BRAF mutations and MSI. The prediction level reached a high accuracy of AUC = 0.955 for the BRAF mutations and AUC = 0.857 for MSI in the training cohort. We verified the AUCs in the validation cohort and achieved AUC = 0.831 and 0.883 for BRAF mutations and MSI, respectively. Conclusions: Our findings suggest that VSQ can appropriately predict BRAF mutation and MSI status in advanced CRC, potentially without performing NGS tests. VSQ may also enable prompt initiation of systemic treatments in CRC patients as well as establish an unprecedented next-generation pathology in the near future.

scholarly journals Rapid BRAF mutation detection in melanoma patients by immunohistochemistry

2017 ◽  
Vol 4 (1) ◽  
pp. 1-5
Author(s):  
László Fülöp ◽  
Katalin Götzer ◽  
Erzsébet Csernák ◽  
Danyil Szergejevics Kuznyecov ◽  
Erika Tóth
Keyword(s):  
Braf Inhibitor ◽  
Pcr Amplification ◽  
Diagnostic Algorithm ◽  
Braf V600e ◽  
Wild Type ◽  
Braf Gene ◽  
Braf Mutations ◽  
Activating Mutation ◽  
Melanoma Patients ◽  
Braf V600 Mutation

The V600E mutation is the most common (~90%) activating mutation of the BRAF gene. BRAF mutations have been frequently investigated in melanoma, colorectal cancer and papillary thyroid carcinoma. The importance of the detection of BRAF mutations has been rising by the routine use of Braf inhibitor therapy. We evaluated the usefulness of the BRAF V600E mutation-specific monoclonal antibody (VE1) in metastatic melanoma patients. To confirm the results of immunohistochemistry (IHC), we used COBAS 4800 BRAF V600 mutation test and PCR amplification followed by Sanger sequencing.36 of 105 patients have wild-type BRAF gene, 64 have V600E mutation and 5 of 105 have V600K mutation. Predicting the mutation only by IHC using VE1 antibody, all 58 positively scored specimen were V600E mutant. The V600K, the wild-type patients and 7 patients from the V600E mutant group scored as negative. Thus the specificity is 100% and the positive predictive value is 1 of the IHC method. After processing our data we could establish a cheaper diagnostic algorithm for rapid detection ofBRAF mutation.

Microsatellite Instability, Mismatch Repair Deficiency, and BRAF Mutation in Treatment-Resistant Germ Cell Tumors

2009 ◽  
Vol 27 (13) ◽  
pp. 2129-2136 ◽  
Author(s):  
Friedemann Honecker ◽  
Hendrik Wermann ◽  
Frank Mayer ◽  
Ad J.M. Gillis ◽  
Hans Stoop ◽  
...  
Keyword(s):  
Germ Cell ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Braf Mutation ◽  
Cisplatin Resistance ◽  
Germ Cell Tumors ◽  
Braf V600e ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Mmr Deficiency

Purpose Mismatch repair (MMR) deficiency and microsatellite instability (MSI) are associated with cisplatin resistance in human germ cell tumors (GCTs). BRAF mutation (V600E) is found in MSI colorectal cancers. The role of RAS/RAF pathway mutations in GCT treatment response is unknown. Patients and Methods Two patient cohorts were investigated: 100 control GCTs (50 seminomas and 50 nonseminomas) and 35 cisplatin-based chemotherapy-resistant GCTs. MMR proteins were analyzed by immunohistochemistry, and eight microsatellite loci were examined for MSI. Tumors were assessed for specific BRAF and KRAS mutations. Results Resistant tumors showed a higher incidence of MSI than controls: 26% versus 0% in two or more loci (P < .0001). All resistant tumors were wild-type KRAS, and two controls (2%) contained a KRAS mutation. There was a significantly higher incidence of BRAF V600E mutation in resistant tumors compared with controls: 26% versus 1% (P < .0001). BRAF mutations were highly correlated with MSI (P = .006), and MSI and mutated BRAF were correlated with weak or absent staining for hMLH1 (P = .017 and P = .008). Low or absent staining of hMLH1 was correlated with promoter hypermethylation (P < .001). Tumors lacking expression of hMLH1 or MSH6 were significantly more frequent in resistant GCTs than in controls (P = .001 and 0.0036, respectively). Within the subgroup of resistant tumors, patients with MSI showed a trend to longer progression-free survival (P = .068). Conclusion We report for the first time a correlation between a gene mutation—BRAF V600E—and cisplatin resistance in nonseminomatous GCTs. Furthermore, a correlation between MMR deficiency, MSI, and treatment failure is confirmed.

BREAKWATER: Randomized phase 3 study of encorafenib (enco) + cetuximab (cetux) ± chemotherapy for first-line (1L) treatment (tx) of BRAF V600E-mutant (BRAFV600E) metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3619-TPS3619
Author(s):  
Scott Kopetz ◽  
Axel Grothey ◽  
Rona Yaeger ◽  
Fortunato Ciardiello ◽  
Jayesh Desai ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Egfr Inhibitor ◽  
Braf Mutations ◽  
Open Label ◽  
Phase 3 ◽  
Previously Treated

TPS3619 Background: Approximately 10% of patients (pts) with mCRC have BRAF mutations (mostly V600E). 1L tx options for BRAFV600E mCRC are limited to cytotoxic chemotherapy ± anti-VEGF or anti-EGFR, or immune checkpoint inhibitors in pts with MSI-H tumors. In Europe, Japan, and USA, the combination of BRAF inhibitor enco + EGFR inhibitor cetux is approved for tx of BRAFV600E mCRC after prior therapy. In BEACON CRC, enco + cetux resulted in a median overall survival (OS) of 9.3 months (95% confidence interval [CI]: 8.0–11.3) and an objective response rate (ORR) of 19.5% (95% CI: 14.5%–25.4%) in previously treated pts with BRAFV600E mCRC (median follow-up: 12.8 months); 57.4% of pts had grade 3/4 adverse events (AEs); 9% discontinued due to AEs. Given the poor prognosis of pts with BRAFV600E mCRC and based on the efficacy and tolerability of enco + cetux from BEACON CRC, BREAKWATER will evaluate efficacy and safety of enco + cetux ± chemotherapy in tx-naive pts with BRAFV600E mCRC. Methods: BREAKWATER is an open-label, global, multicenter, randomized, phase 3 study with a safety lead-in (SLI). Approximately 60 and 870 pts will be enrolled in the SLI and phase 3 parts of the study, respectively. Pts must have BRAFV600E mCRC (determined using tumor tissue or blood); ECOG performance status 0/1; and adequate bone marrow, hepatic, and renal function. Pts in the SLI must have evaluable disease (RECIST v1.1) and have received ≤ 1 prior tx regimen; those previously treated with a BRAF or EGFR inhibitor, or both oxaliplatin and irinotecan, will be excluded. Pts in the phase 3 study must have measurable disease and be tx naive for metastatic disease. Study tx and endpoints are shown in the table. Enrollment began on 6 January 2021. Clinical trial information: NCT04607421. [Table: see text]

Whole Tumor Capsule is Prognostic of a Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer

2021 ◽  
Author(s):  
Carlotta Giani ◽  
Liborio Torregrossa ◽  
Ramone Teresa ◽  
Romei Cristina ◽  
Antonio Matrone ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Braf V600e ◽  
Braf Mutations ◽  
Biological Behaviour ◽  
Non Invasive ◽  
Good Outcome ◽  
Predictive Role ◽  
Pathological Behavior

Abstract Context Tumour capsule integrity is becoming a relevant issue to predict the biological behaviour of human tumours, including thyroid cancer. Aim To verify if a whole tumour capsule in the classical variant of PTC (CVPTC) could have a predictive role of a good outcome as for follicular variant (FVPTC). Methods FVPTC (n=600) and CVPTC (n=554) cases, were analysed. We distinguished encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and non-invasive (En-FVPTC and En-CVPTC) tumours, according to the invasion or integrity of tumour capsule, respectively. Cases without tumour capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). Sub-group of each variant was evaluated for BRAF mutations. Results E-FVPTC was more frequent than E-CVPTC (p&lt;0.0001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. 177/614 (28.8%) cases were BRAF  V600E-mutated and 10/614(1.6%) carried BRAF-rare alterations. Significantly higher rate of En-CVPTC (22/49,44.9%) than En-FVPTC (15/195,7.7%) (p&lt;0.0001) were BRAF  V600E-mutated. Conclusions En-CVPTC is less prevalent than En-FVPTC. However, they have a good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumour capsule also in CVPTC. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (i.e, NIFTP) could be envisaged.

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