التفاصيل البيبلوغرافية
| العنوان: |
Characterization of the minimal residual disease state reveals distinct evolutionary trajectories of human glioblastoma. |
| المؤلفون: |
Qazi, Maleeha A., Salim, Sabra K., Brown, Kevin R., Mikolajewicz, Nicholas, Savage, Neil, Han, Hong, Subapanditha, Minomi K., Bakhshinyan, David, Nixon, Allison, Vora, Parvez, Desmond, Kimberly, Chokshi, Chirayu, Singh, Mohini, Khoo, Amanda, Macklin, Andrew, Khan, Shahbaz, Tatari, Nazanin, Winegarden, Neil, Richards, Laura, Pugh, Trevor |
| المصدر: |
Cell Reports; Sep2022, Vol. 40 Issue 13, pN.PAG-N.PAG, 1p |
| مستخلص: |
Recurrence of solid tumors renders patients vulnerable to advanced, treatment-refractory disease state with mutational and oncogenic landscape distinctive from initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profile barcoded tumor stem cell populations through therapy at tumor initiation, MRD, and recurrence in our therapy-adapted, patient-derived xenograft models of glioblastoma (GBM). Tumors show distinct patterns of recurrence in which clonal populations exhibit either a pre-existing fitness advantage or an equipotency fitness acquired through therapy. Characterization of the MRD state by single-cell and bulk RNA sequencing reveals a tumor-intrinsic immunomodulatory signature with prognostic significance at the transcriptomic level and in proteomic analysis of cerebrospinal fluid (CSF) collected from patients with GBM. Our results provide insight into the innate and therapy-driven dynamics of human GBM and the prognostic value of interrogating the MRD state in solid cancers. [Display omitted] • Therapy-adapted model allows for temporal profiling of glioblastoma (GBM) recurrence • GBM recurrence arises from pre-existing or therapy-driven clonal populations • Post-therapy minimal residual disease (MRD) state is identified and characterized • MRD-derived tumor-intrinsic immunomodulatory signature is prognostic for survival Using a therapy-adapted model and cellular barcoding, Qazi et al. show that glioblastoma recurrence arises from clonal populations that have pre-existing or therapy-driven fitness advantage. Further characterization of the post-therapy minimal residual disease state identifies a tumor-intrinsic immunomodulatory signature that is prognostic for glioblastoma survival. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
