Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Autor: Shireman JM; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., White Q; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Agrawal N; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA., Ni Z; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Chen G; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Zhao L; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Gonugunta N; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Wang X; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Mccarthy L; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Kasulabada V; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Pattnaik A; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Ahmed AU; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA., Miller J; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Kulwin C; Goodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USA., Cohen-Gadol A; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Payner T; Goodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USA., Lin CT; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Savage JJ; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Lane B; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Shiue K; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA., Kamer A; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA., Shah M; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA., Iyer G; Department of Human Oncology, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Watson G; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA., Kendziorski C; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Dey M; Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 Apr 24. Date of Electronic Publication: 2023 Apr 24.
DOI: 10.1101/2023.04.15.23288491
Abstrakt: Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.
Databáze: MEDLINE