KDM5C mutation

an increased incidence of KDM5C mutations, which, in common with increased PBRM1 alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.

Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.

Validation in the IMmotion151 trial revealed a similar correlation with increased angiogenesis and the PFS of patients in the VEGFR-TKI-arm was the longest in PBRM1&KDM5C mutated cases, intermediate for only PBRM1 or only KDM5C mutated patients and the shortest in non-mutated cases (P=0.009 and 0.025, for PBRM1&KDM5C and PBRM1 versus non-mutated cases). In conclusion, somatic PBRM1 and KDM5C mutations are common in patients with metastatic ccRCC and likely cooperate increasing tumor angiogenesis and VEGFR-TKI-based antiangiogenic therapy benefit.

B7H3 was negative in all tumors. Morphologic findings in this small cohort may suggest why PBRM1 mutation does not correlate with decreased survival, whereas BAP1 mutation usually predicts poor outcomes.

SMARCA4-UTs are aggressive malignant neoplasms associated with dismal outcomes, and our study shows that it is possible to diagnose this entity on limited samples. Since most cases present with metastasis, majority will only be diagnosed on cytology and small biopsies. Therefore, awareness of the cytologic features is paramount.

Cancer Genome Atlas (TCGA) pan-cancer analysis suggested that the association of KMT2C/BCOR/KDM5C mutations with ICB response observed here might not result from DNA repair defects. In conclusion, our data indicate that KMT2C/BCOR/KDM5C mutation has the potential to serve as a predictive biomarker, alone or combined with PD-L1 expression or TMB, for ICB therapy in NSCLC.

This work revealed that a histone modifier gene inactive mutation reprogramed glycogen metabolism and helped to explain the long-standing puzzle of male predominance in human cancer. In addition, our findings may suggest the therapeutic value of targeting glycogen metabolism in ccRCC.

This study provides evidence that there are associations between somatic mutations, such as SETD2 and KDM5C, and macrophage and T cell infiltration patterns in the TIME in ccRCC. Sequencing-derived xCell enrichment scores from TCGA, CPTAC, and AVATAR were discordant with the IF-derived immune cell infiltration findings. These novel associations have the potential to inform precision research and immunotherapeutic treatment strategies.

This study provides evidence that common somatic mutations in ccRCC, such as SETD2, PBRM1, and KDM5C, are associated with distinct immune infiltration patterns within the TIME.

This study demonstrates for the first time an increased amount of TAT, especially VAT, in the ccRCC-VHL and ccRCC-KDM5C groups. The effect was greater for the ccRCC-KDM5C group.

In the validation cohort, the immunotherapy efficacy of patients with KDM5C mutations was better than that of KDM5C wild-type patients, with median overall survival 21 months (95% CI, 12.4 to 29.6) and 11 months (95% CI, 8.9 to 13.1) (hazard ratio for death, 0.63; 95% CI, 0.26 to 1.53). Conclusion KDM5C mutations are associated to better efficacy of immunotherapy and have potential value for guiding clinical practice.

Legal entity responsible for the study: The authors. Funding: Has not received any funding.

This study provides evidence that common somatic mutations in ccRCC, such as SETD2, PBRM1, and KDM5C, may be associated with distinct immune infiltration patterns within the TIME. These novel associations have the potential to inform precision research and immunotherapeutic treatment strategies.Funding: Urology Care Foundation Research Scholar Award Program and Society for Urologic Oncology (to BJM); the United States Army Medical Research Acquisition Activity Department of Defense (KC180139 to BJM);