Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

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., Ni Z; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Mohanty C; Department of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA., Cai Y; 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., Agrawal N; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, 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 Clinical Radiology and Imaging Sciences, 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:	IScience [iScience] 2024 Mar 27; Vol. 27 (4), pp. 109601. Date of Electronic Publication: 2024 Mar 27 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109601
Abstrakt:	Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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