ARID2 mutation

Remarkably, this gene signature is conserved in melanoma patients with ARID2 mutations. In sum, we demonstrate a unique role for PBAF in generating accessibility for a silencing transcription factor at repressed chromatin, with important implications for disease.

Melanoma patients with ARID mutations exhibited higher prevalence of markers associated with ICI response, including TMB-H, and immune-related signatures. Our data also suggests improved survival outcome in patients with ARID2 mutations, irrespective of anti-PD1 therapy.

Conclusions Melanoma patients with ARID mutations exhibited higher prevalence of markers associated with ICI response, including TMB-H, PD-L1 and immune-related signatures. Our data also suggests improved survival outcome in patients with ARID2 mutations, although no additional OS benefit was observed with anti-PD-L1 therapy.

The research presented in this study shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with lung adenocarcinoma.

Altogether genomic, biological and clinical findings highlight HR/HER2 dnMBC as a peculiar entity as compared with rMBC and deserve a dedicated treatment algorithm. This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

Furthermore, mutational profiles, such as top frequently mutated genes and mutational signatures of patients with various EGFR subtype mutations were significantly different. Our study analyzed the mutational landscape of NSCLC patients harboring cEGFR and uEGFR mutations, revealing specific genomic characteristics associated with uEGFR mutations that might explain the poor prognosis of first-generation EGFR-TKIs.

In summary, the mutational landscape of 5 major SWI/SNF pathway genes were classified. The research presented also shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with SWI/SNF mutant lung adenocarcinoma.

cSCC-PDX models responded well to both eribulin and cisplatin treatments. In addition, we developed a unique cSCC-PDX model that maintains the characteristics of a patient's tumor. This PDX model could help researchers who are exploring novel therapeutic strategies for cSCC.

Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors.

Interestingly, JQ1, a selective inhibitor of bromodomain protein BRD4, uniquely suppressed the growth of ARID2- deficient HCC cells...However, as both ARID2 and BRD4 are disrupted, the expression of these DNA repair-related genes in response to DNA damage are hindered, resulting in DSB accumulation and cell apoptosis. Taken together, this study discloses that BRD4 inhibition may induce synthetic lethality in ARID2-deficient HCC cells, which might provide a potential therapeutic strategy for HCC patients with ARID2 mutations.

Finally, a nomogram was established to guide the clinical use of ICIs. The results show that patients with NSCLC who have ARID1A, ARID1B, and ARID2 mutations of the SWI/SNF complex were more likely to benefit from ICI therapy.

Seven potential MBC driver mutations showed similar preferential enrichment in specific metastatic sites. This large-scale study identified new MBC genetic alterations according to various metastatic sites and highlights their potential role in breast cancer organotropism.

No abstract available

Moreover, we demonstrated that ARID2 deficiency impairs DNA repair, enhancing the sensitivity of the cells to DNA-damaging agents. Our findings support that ARID2 is a bona fide tumor suppressor gene in lung cancer that may be exploited therapeutically.