Epigenetic inactivation of HOXA11 as a novel functional tumor suppressor for renal cell carcinoma

Wang, L.; Cui, Y.; Sheng, J.D.; Yang, Y.; Kuang, G.Y.; Fan, Y.; Jin, J.; Zhang, Q.

doi:10.1016/s1569-9056(17)31034-5

Cited by 1 publication

(1 citation statement)

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“…In addition to the 14 known regulators of ferroptosis, gbmMINER predicted that this process was also putatively regulated by an additional 15 TFs, including ETV7, HOXA11, LEF1, LHX1, LHX3, NFATC4, BPTF, POU3F3, ELF3, SOX11, CTCF, SOX3, SOX5, SRF, and ELF5 (Supplementary Table 4). Consistent with their gbmMINER predicted roles in activating ferroptosis-driver genes, ELF5, SOX11 and HOXA11 were previously demonstrated to act as tumor suppressors in many cancers [64][65][66][67][68] . Conversely, consistent with its gbmMINERpredicted suppressor role, NFATC4 is known to promote oncogenesis 69…”

Section: Better Prognosis Of Idh1 Atrx and Tp53 Mutations Likely Mani...supporting

confidence: 52%

An atlas of causal and mechanistic drivers of interpatient heterogeneity in glioma

Turkarslan,

He,

Hothi

et al. 2024

Preprint

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Grade IV glioma, formerly known as glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor, and its treatment remains challenging in part due to extensive interpatient heterogeneity in disease driving mechanisms and lack of prognostic and predictive biomarkers. Using mechanistic inference of node-edge relationship (MINER), we have analyzed multiomics profiles from 516 patients and constructed an atlas of causal and mechanistic drivers of interpatient heterogeneity in GBM (gbmMINER). The atlas has delineated how 30 driver mutations act in a combinatorial scheme to causally influence a network of regulators (306 transcription factors and 73 miRNAs) of 179 transcriptional "programs", influencing disease progression in patients across 23 disease states. Through extensive testing on independent patient cohorts, we share evidence that a machine learning model trained on activity profiles of programs within gbmMINER significantly augments risk stratification, identifying patients who are super-responders to standard of care and those that would benefit from 2nd line treatments. In addition to providing mechanistic hypotheses regarding disease prognosis, the activity of programs containing targets of 2nd line treatments accurately predicted efficacy of 28 drugs in killing glioma stem-like cells from 43 patients. Our findings demonstrate that interpatient heterogeneity manifests from differential activities of transcriptional programs, providing actionable strategies for mechanistically characterizing GBM from a systems perspective and developing better prognostic and predictive biomarkers for personalized medicine.

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Section: Better Prognosis Of Idh1 Atrx and Tp53 Mutations Likely Mani...supporting

confidence: 52%

An atlas of causal and mechanistic drivers of interpatient heterogeneity in glioma

Turkarslan,

He,

Hothi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Epigenetic inactivation of HOXA11 as a novel functional tumor suppressor for renal cell carcinoma

Cited by 1 publication

References 0 publications

An atlas of causal and mechanistic drivers of interpatient heterogeneity in glioma

An atlas of causal and mechanistic drivers of interpatient heterogeneity in glioma

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