Thirty-six tumor tissues from BRAF wild-type melanoma patients at Seoul National University Hospital (SNUH) were collected and deep-sequenced using the SNUH FIRST-Cancer NGS panel to assess single nucleotide variants, small insertions/deletions, copy number variations, and structural variations to estimate tumor mutation burden (TMB).
Melanoma treatment have been revolutionized since 2010 by the development of immune checkpoint inhibitors, and, for BRAF-mutated melanoma, targeted therapies based on BRAF and MEK inhibitors, which is a model of effective targeted therapy in cancer.
Associations between BRAFV600E and TERT promoter mutations and clinicopathological features, Tumor-Node-Metastasis stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association 2015 criteria and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system.Median follow-up was 120 months.
For this study, we collected clinical information from PTC patients and monitored the levels of urinary iodine, LC3-II, and caspase-3 in cancer tissue, and BRAF kinase in peripheral blood from PTC patients.
In serrated adenomas, BRAF-V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.
The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade.
PGC1α-negative papillary cancer was associated with BRAFV600E mutation, large tumor size, extrathyroidal or lymphovascular invasion, lymph node metastasis, and advanced stage.
This study shows for the first time that E2F1 has a cancer protective role in oncogenic BRAF-activated melanoma cells and that loss of E2F1 can allow disease progression through a novel mechanism of E2F1-mediated MYLK regulation.
The development of BRAF and MEK inhibitors (BRAFis and MEKis) and immune checkpoint inhibitors have changed the management of advanced stage melanoma and improved the outcomes of patients with this malignancy.
Utility of targeting the MAPK pathway has been demonstrated by clinical responses to inhibitors of MEK1/2 or RAF kinases in some mutant BRAF-activated malignancies.
Thyroid carcinomas (TCs) bearing BRAF mutations represent approximately 29-83% of human thyroid malignancies and, differently from melanomas, are less sensitive to BRAF inhibitors and develop primary or acquired resistance due to mutational events or activation of alternative signaling pathways able to reactivate ERK signaling.
In this issue of Cancer Cell, Tao et al. provide compelling evidence that aging-like DNA methylation of multiple CpG islands, the CpG island methylator phenotype (CIMP), produces a cellular context that can tolerate BRAF activation avoiding senescence by dedicating 5-month culture of colon-derived organoids to epigenomic and stemness analysis.
Our experiments highlight key differences between oncogenic BRAF and KRAS in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Recent high-throughput-sequencing of cancer genomes has identified oncogenic mutations in the B-Raf genetic locus as one of the critical events in melanomagenesis.
Here, we show that endothelial cell-restricted ablation of BRAF, a kinase frequently activated in cancer, prevents vascular leaking as well metastatic spread.