BRAF exon 15 mutation

The study's findings indicate a rising frequency of mutations in these genes in Iran, highlighting the need to screening mutations in the main exons of all three genes for effective colorectal cancer treatment strategies.

Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

The anti-tumor effects of LY3009120 were observed in nine melanoma cell lines, indicating the potential feasibility of experimental trials with LY3009120. The present study reveals that the irradiation-resistant canine metastasis cells (cRGO1.2) harboring the NRAS p.G13R mutation are significantly LY3009120-sensitive, while the equine metastases-derived eRGO6 cells show significant resistance to LY3009120, which make them both valuable tools for studying resistance mechanisms in comparative oncology.

P2, N=240, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jun 2024 --> Nov 2024

P1; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

This is the first case of the novel nonclassical genomic variant of BRAF. Our study extends the spectrum of BRAF mutations. The patient had a favorable response to microwave ablation, indicating that in spite of the association between this mutation and high-grade malignant phenotype, this genomic variant of BRAF did not have a detrimental effect on the response of clinical treatment.

Pediatric epithelial neoplasms with features of MA that show partial encapsulation and/or modest mitotic activity may be classified as MAs. Although BRAF mutation supports the diagnosis of MA, it is not required for the diagnosis.

We found a novel variant in BRAF gene. The p. Ser616Thr (c.1846T>A) mutation was not previously reported and we conclude that other new mutations can be identified in KRAS and BRAF which may lead to colorectal cancer.

Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.

RAS mutation seems to be related to poor prognosis and increased risk of recurrence in rectal cancer patients undergoing radical surgery after chemo-radiotherapy.

Though alterations in the EGFR and ALK genes usually present a favorable prognosis, our work suggests that some of their variants are associated with a poor survival. This study also reveals other mutations like alterations on PIK3CA and CTNNB1 genes, which may impact lung cancer prognosis and will require further exploration.

Our study revealed the prevalence of CRC biomarkers mutations in Iranian patients and emphasized the role of KRAS and PIK3CA on shorter overall survival rates in this population.

"The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test."

Furthermore, the SensiScreen® FFPE BRAF qPCR Assay identified the specific change in the amino acid. The SensiScreen® FFPE BRAF qPCR Assay will contribute to a more specific, time and cost saving approach to better identify and characterize mutations in patients affected by cancer, and consequently permits a better BRAF characterization that is fundamental for therapy decision.

We highlighted the feasibility of PD-L1 assessment on residual CB material from metastatic melanomas previously tested for BRAF and NRAS mutations. Moreover, we pointed out that FNC needle rinses may be an alternative sources of nucleic acids for molecular testing, preserving CB material for ICC evaluation.

P2, N=240, Active, not recruiting, Southwest Oncology Group | Trial primary completion date: Nov 2023 --> Nov 2022

Novel BRAF mutations and V600E were frequently detected in thyroid cancer of Libyan patients; this suggests a potential role of these novel mutations in carcinogenesis and in anti-EGFR therapy resistance.

P2, N=240, Active, not recruiting, Southwest Oncology Group | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Nov 2022 --> Nov 2023

The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1/PMS2/MSH6 cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern.

Molecular analysis found a somatic p.Asn581Ser (c.1742A>G) point mutation in exon 15 of BRAF and a p.Arg80Ter (c.238C>T) germline variant of CDKN2A, a predisposing mutation to melanoma. This case report highlights the importance of clinical, pathologic, and molecular correlation.

This pediatric and young adult BRAF-positive cohort (14% of tested samples) included primarily low-grade CNS tumors, followed by PTC and histiocytosis, indicating that a significant fraction of pediatric tumors may benefit from BRAF inhibitor therapy. The rate of fusion and SNV positivity was nearly equal, though varied by tumor type, demonstrating the utility of a comprehensive panel targeting both DNA and RNA.

In conclusion, the assessment of these mutations suggests that CRC patients from southeast Romania exhibit a mutation profile similar to other populations. These results could contribute to creating a better method of qualifying patients for molecularly targeted therapies and obtaining better screening strategies.

P1; Recruiting --> Active, not recruiting | N=40 --> 18

P2, N=240, Active, not recruiting, Southwest Oncology Group | Recruiting --> Active, not recruiting | N=130 --> 240

Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS-/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and <15%, respectively, indicating easy misdetection by Sanger sequencing when the mutation rate is between 5 and 15%. ddPCR has higher sensitivity than Sanger sequencing and we propose ddPCR as a supplement to Sanger sequencing in molecular testing of BRAF using FNAB samples.

P2, N=34, Completed, Grupo Espanol Multidisciplinario del Cancer Digestivo | Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> Dec 2021

In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.

P1; Trial completion date: Jan 2023 --> Jan 2024 | Trial primary completion date: Jan 2023 --> Jan 2024

Gene phenotypes of mucosal melanoma in different locations has differences. Lesions in the nasal cavity and paranasal sinus should be assessed separately from other parts such as the nasopharynx.

"The targeted capture sequencing test can support comprehensive molecular analysis needed for TKIs treatment, which is promising to be clinically applied for the improved precision treatment of NSCLC."

HRAS T81C polymorphism may be involved in the etiopathogenesis of DTC in a Pakistani cohort. Furthermore, testing for the BRAF mutation may be useful for selecting initial therapy and follow-up monitoring.

Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

However, c-MET-high in the primary tumors was not significantly associated with longer survival compared with c-MET-low tumors. Further studies are required to investigate c-MET as potential molecular marker of progression and to test the possibility of its incorporation as a new therapeutic target.

Given the interaction seen in this study, it may be worth considering the MSI status while looking for methylation markers in CRC. The study also indicates an opportunity for potential use of certain immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI.

P2, N=130, Recruiting, Southwest Oncology Group | Trial primary completion date: Apr 2022 --> Nov 2022

BRAF V600E mutation-positive papillary thyroid carcinomas consistently showed all characteristic nuclear features, such as nuclear crowding, overlapping, and grooves. Considering the greater prevalence in the younger age group, the importance of mutation surveillance in PTCs for a total thyroidectomy may be warranted in mutation-positive patients.

Then, most of the cases were diagnosed in the advanced stages of the disease and were represented by high-grade adenocarcinomas. This article demonstrates the feasibility of analysis of the entire exon 15 of BRAF gene in CRC patients regardless of tumor localization.

P2, N=23, Terminated, Hellenic Cooperative Oncology Group | Active, not recruiting --> Terminated; It was considered that the recruitment of the remaining 10 patients required of the trial will not be possible soon.

It is interesting to note that signet ring cell carcinoma does not portend a worse prognosis for patients with high TIL levels. Combining use the grade of TIL status with the WHO grade of the entire tumor can help identify patients with a high risk of recurrence more accurately.