Bulk RNA-seq of U251N orthotopic glioblastoma xenografts in athymic RNU/RNU rats before and after MRI-guided laser interstitial thermal therapy (LITT)

Laser interstitial thermal therapy (LITT) is increasingly used for deep-seated and recurrent glioblastoma, but the transcriptional state of cells that survive the sublethal thermal penumbra and seed recurrence is poorly defined. We performed bulk RNA-seq on matched primary (pre-LITT) and recurrent (post-LITT) tumors from a U251N orthotopic xenograft in athymic RNU/RNU rats treated with MRI-guided LITT. Reads were sorted into human (graft) and rat (host) streams with xengsort to isolate the human tumor transcriptome from host signal. Recurrent tumors showed a pronounced translational shutdown and integrated-stress-response activation, with a shift toward the Garofano Mitochondrial molecular subtype, nominating the translation/ISR axis as a candidate target for LITT-adjuvant therapy.