BRAF D594G

Furthermore, TP53, LRP1B, STK11, SPTA1and MAGI2 were significantly over-mutated in Class II and III (p<0.06) and SETD2 is over-mutated in Class I (p<0.001), might suggesting relatively poor prognosis in NSCLC patients. Conclusions The characteristics of Chinese NSCLC were further explored, including BRAF mutation types, the incidence of related co-mutations and TMB value, which is helpful to formulate targeted therapy strategies to adapt to different types of BRAF mutation functions according to their genomic and clinical characteristics.

The findings of this cohort study suggest that there are broad differences among organoids with different BRAF variant subtypes in sensitivity to BRAF or MEK inhibitors. Identifying and classifying BRAF variants may be able to help guide precise treatment for patients with ICC.

We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

aBRAF mutations have historically been considered a favorable prognostic marker in mCRC. Co-mutation with RAS is frequent for both classes and portends poor survival in our real-world cohort. Furthermore, early onset aBRAF mCRC is associated with more aggressive disease.

This is a single center experience from an Indian NSCLC cohort and shows higher prevalence of non-V600E than V600E mutation reported in literature. This may be attributed to increased use of NGS testing revealing otherwise missed alterations on sequential single gene testing.

Conclusion Our results - on a small number of patients - suggest that patients with rare BRAF mutations may have inferior survival outcomes with first line targeted treatment, compared with patients with classical BRAF mutations. Impact statement Our findings add to the limited clinical knowledge on rare BRAF mutations in melanoma and may help guide treatment decisions on this small subset of patients.

Vemurafenib and dabrafenib have already been approved for the treatment of melanoma, NSCLC and colorectal carcinoma. BRAF gene mutations, especially BRAF non-V600, was extensively mutated in Chinese multiple cancer types. Our revealed the potential targeted therapeutic strategies among non-V600 population with solid tumors should be considered in further study.

Preliminary data confirmed the safety of B+E and demonstrated evidence of anti-tumor activity in advanced cancer pts with non-V600E BRAF mts. Enrolment in the BEAVER trial is ongoing.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Conclusion BRAF D595G mutations, commonly found in colorectal cancer, are “kinase dead mutations” capable of upregulating the MAPK signalling pathway. This demonstration of the identification and sensitive plasma detection of a common “drugable” target, emphasises the impact of precision medicine in the management of rare tumours and its potential contribution towards novel therapeutic strategies in this field.

Treatment regimens: standard rituximab-containing (n=15) and targeted drugs (n=11). The Lymphoid Targeted NGS Panel was designed as a comprehensive gene panel and covered 117 genes, part of which plays a core role in cellular pathways...Conclusion The obtained data demonstrate the possibility of applying NGS in clinical practice and the approbation of The Lymphoid Targeted NGS Panel. Whereas the clinical significance of some mutations is currently uncertain, further research using NGS technology is required.

One patient with V600E mutation received vemurafenib . The other patient with a nonV600E mutation (V600_601delins, detected on NGS) received combination dabrafenib-trametinib with an ongoing partial response at 6 months... This single centre study depicts distinct clinicopathologic features in Indian patients with BRAF mutant NSCLC . The higher prevalence of non-V600E mutation may be attributed to increased use of broader panel based NGS testing as opposed to sequential single gene testing . One of the patients with a non-V600E mutation responded to targeted therapy, hence clinicians should be aware of this spectrum of potentially targetable BRAF mutations.

This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy...As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.

All patients had indications for starting treatment: FCR (n=7), RB (n=6), ibrutinib (n=3), venetoclax (n=1), acalabrutinib (n=5), combination of venetoclax and acalabrutinib (n=2). The data obtained from a pilot study demonstrate the possibility of using NGS technology in clinical practice. The assessment of the mutational status of pts with CLL using NGS correlates with the clinical parameters of pts. Considering that there is currently no information about prognostic significances of identified mutations, additional research is required.

Additionally, we show that BRAFD594G:CRAF heterodimers bypass autoinhibitory P-loop phosphorylation, which might contribute to longer duration of MAPK pathway signaling in cancer cells. Lastly, we propose that the dimer interface of BRAF:CRAF heterodimer may represent a promising target in the design of novel anticancer therapeutics.

"In BRAF-mutant NSCLC, clonality is higher in known functional mutations and may allow identification of VUS more likely to be oncogenic drivers. Our data indicate certain non-V600 mutations are responsive to MEK and BRAF inhibitors. This integration of genomic profiling and drug sensitivity may guide treatment for BRAF-mutant NSCLC."

The addition of bevacizumab may prolong survival in aBRAFmt, but aBRAFmt may be a negative predictive marker for EGFRmAb efficacy...The study sponsors had no role in the design and conduct of the study, collection, analysis and interpretation of the data or decision to submit the manuscript for publication. PRCRC: has been funded by the Swedish Cancer Society.