MAP3K1 mutation

In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.

Additionally, inactivating PPP2R3C mutations and activating MAP3K1 mutations both cause congenital syndromes characterized by gonadal dysgenesis.22,23,24,25,26,27,28 As a syndromic PPP2R3C variant is defective in centriolar localization and binding to centriolar protein FOP, we propose that imbalanced activity of this centrosomal kinase-phosphatase pair is the shared cause of these disorders. Thus, our findings reveal a new centrosomal phospho-regulatory module, shed light on disorders of gonadal development, and illustrate the power of systems genetics to identify previously unrecognized gene functions.

Cancer panel testing for cfDNA identified prognostic and predictive biomarkers for palbociclib add-on therapy after acquiring fulvestrant resistance in patients with HR+/HER2- ABC/MBC.

The Cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.

In addition, analyses of collagen-high patients from the METABRIC study indicated that most cases presented with PIK3CA, CBFB and MAP3K1 mutations, while through the g.Profiler software we identified collagen-high relevant gene signatures that encompassed gene ontology terms related to tissue development, extracellular matrix organization and cell migration. Collectively, our preliminary results indicate that ECM collagen deposition in breast cancer is characteristic of low-grade tumors with a better differentiation and possibly with a favorable prognosis.

We found similar mutational profiles between primary and paired recurrent tumors, suggesting that genomic features may be retained during local recurrence.

DNA MP yielded a match with DLGNT though somewhat incongruent radiographic findings were present. These observations suggest that DLGNT may in fact originate from an intramedullary lesion with a propensity for leptomeningeal dissemination.

Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.

For breast cancer patients eligible for inclusion, patients were allocated to 2 cycles of chemotherapy using nab-paclitaxel with carboplatin...Group C were received dalpiciclib, letrozole and adebrelimab plus goserrelin if patient was premenopausal... From Nov 16, 2020 to Jun 10, 2022, 121 patients were enrolled... Neoadjuvant chemotherapy and neoadjuvant endocrine therapy are not mutually exclusive. The overall treatment strategy did not improve the efficacy, but there is still a possibility that some people can get an improvement from the strategy adjustment. Precision analysis may yield the characteristics of patients who would benefit from this shift in treatment strategy.

Moreover, the MAP3K1 methylation levels were reduced in primary breast cancer tissue, compared with normal tissue. Thus, the present findings identified MAP3K1 mutations in Chinese patients with breast cancer, and compared MAP3K1 mutations between the cohorts from Western and Eastern countries.

Besides identifying several rare or novel kinase fusions genes, our analysis also revealed various additional mutations including recurrent PIK3CA point mutations. Although their significance is unknown, they might be responsible for progression of tumors with LG morphology (LNT, FTPH) into tumors with HG morphology and/or acquisition of a more aggressive biological potential. Targeted therapy is effective and significantly aids in successful treatment.

The PALLET phase II randomized neoadjuvant trial of letrozole (LET) ± palbociclib (PALBO) in postmenopausal ER+HER2- primary breast cancer showed that suppression of proliferation as measured by Ki67 was significantly greater with addition of PALBO to LET but did not result in all patients achieving complete cell-cycle arrest, indicating intrinsic resistance in some patients. We observe, confirming previous studies, an association of CDK4/6 inhibitor resistance, high expression of CCNE1 and genes related to interferon gamma signalling. We show that there is an overlap between resistance mechanisms and TP53 mutations. However, ER+HER2- patients with TP53 mutations may still benefit from PALBO adding to suppression of proliferation compared to LET-only treatment.

Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making.

CCL5 and the other MEKK1-dependent chemokines are ligands for the GPCR CCR5, and we show that the CCR5 antagonist Maraviroc strongly inhibits fibroblast-induced tumor cell migration. Finally, we report that fibroblast growth factor 5 (FGF-5) is secreted by MDA-MB 231 cells, that FGF-5 activates MEKK1 effectors ERK1/2 and NFκB in fibroblasts, and that chemical inhibition of NFκB inhibits CCL5 expression. Our results suggest that MEKK1 contributes to the formation of a breast tumor microenvironment that supports metastasis by promoting expression of stroma cell chemokine genes in response to tumor cell-induced paracrine signaling.