Overall, our results suggest a molecular sub-cluster of colon cancer cells with low CDX2 and VDR expression is sensitive to chemotherapy, BRAF inhibitors and PI3K-mTOR inhibitors treatment and provide an example of translation of cancer classification to subgroup guided therapies.
Eleven of 31 cases with an indeterminate cytologic diagnosis and 9 of 12 cases that were suspicious for malignancy had somatic mutations, including the BRAFV600E mutation, which is highly definitive for papillary thyroid carcinoma (PTC).
Increasing evidence reported that aberrant expression of <i>BRAF activated non-coding RNA</i> (<i>BANCR</i>) was involved in the tumorigenesis and progression of various malignancies.
Reverse Phase Proteomic Array (RPPA, MD Anderson Cell Lines Project), RNAseq (Cancer Cell Line Encyclopedia) and vemurafenib sensitivity (Cancer Therapeutic Response Portal) data for BRAF-V600Ecancer cell lines were curated.
BRAF mutations were confirmed as highly specific but not able to improve cytological diagnosis, while RAS testing proved effective in assessing malignancy in nodules with indeterminate and benign cytology.
Twelve of the 33 cell lines were trametinib-sensitive (IC<sub>50</sub> < 32 nmol/L), all 12 exhibited constitutive or serum-activated ERK1/2 phosphorylation, and 8 carried MAPK pathway cancer driver variants: NF1(2), BRAF(3), N/KRAS(3).
Furthermore, our analysis carried out through the Genomic Data Commons (GDC) Data Portal shows the evidence that hsa-mir-132 is significantly associated with clinical outcome in melanoma cancer genomic data sets of BRAF-mutated patients.
A number of BRAF fusions with different 5' gene partners and BRAF exon breakpoints have been described, but the effects of different partners and breakpoints on cancer phenotypes and treatment responses has not been well characterized.
We compared several criteria such as cancer type, sample type, organ of origin and percentage of tumour cells between samples with non-contributive or contributive EGFR, KRAS, NRAS and BRAF mutation analyses.
Also highlighted are the functional consequences of aberrant splice variants (<i>BCR-Abl35INS</i>, <i>BIM-γ</i>, <i>IK6</i>, <i>p61 BRAF V600E</i>, <i>CD19-∆2</i>, <i>AR-V7</i> and <i>PIK3CD-S</i>) in promoting resistance to cancer targeted therapy or immunotherapy.
Methods In this phase II, open-label trial, patients with predefined BRAFV600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death.
In contrast, APC missense mutations that were rare in conventional pathway adenomas and cancers (3% in BRAF wild-type cancers) were more frequent in BRAF mutant cancers with microsatellite instability (32%).
RAF inhibitor LY3009120 sensitizes RAS or BRAF mutant cancer to CDK4/6 inhibition by abemaciclib via superior inhibition of phospho-RB and suppression of cyclin D1.
This is true for targeted therapies using tyrosine kinase inhibitors for EGFR or BRAF mutant cancers, but is also an increasingly recognized problem for immunotherapies.
Consistently, inhibition of SHP2 (also known as PTPN11), which links receptor tyrosine kinase signaling to the RAS-RAF-MEK-ERK pathway<sup>11,12</sup>, was shown to be ineffective in KRAS-mutant or BRAF-mutant cancer cell lines<sup>13</sup>.
TP53 and U2AF1 mutations have been implicated in other myelomonocytic malignancies and we hypothesized that mutations in these genes may cosegregate in LCH patients according to BRAF mutation status.