Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure
Summary: 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 w...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422400823X |
| _version_ | 1797215898097942528 |
|---|---|
| author | Jack M. Shireman Quinn White Zijian Ni Chitrasen Mohanty Yujia Cai Lei Zhao Namita Agrawal Nikita Gonugunta Xiaohu Wang Liam Mccarthy Varshitha Kasulabada Akshita Pattnaik Atique U. Ahmed James Miller Charles Kulwin Aaron Cohen-Gadol Troy Payner Chih-Ta Lin Jesse J. Savage Brandon Lane Kevin Shiue Aaron Kamer Mitesh Shah Gopal Iyer Gordon Watson Christina Kendziorski Mahua Dey |
| author_facet | Jack M. Shireman Quinn White Zijian Ni Chitrasen Mohanty Yujia Cai Lei Zhao Namita Agrawal Nikita Gonugunta Xiaohu Wang Liam Mccarthy Varshitha Kasulabada Akshita Pattnaik Atique U. Ahmed James Miller Charles Kulwin Aaron Cohen-Gadol Troy Payner Chih-Ta Lin Jesse J. Savage Brandon Lane Kevin Shiue Aaron Kamer Mitesh Shah Gopal Iyer Gordon Watson Christina Kendziorski Mahua Dey |
| author_sort | Jack M. Shireman |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-24T11:37:23Z |
| format | Article |
| id | doaj.art-828ec409f6884148a8d4d17d849d56c6 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T11:37:23Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-828ec409f6884148a8d4d17d849d56c62024-04-10T04:29:22ZengElsevieriScience2589-00422024-04-01274109601Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failureJack M. Shireman0Quinn White1Zijian Ni2Chitrasen Mohanty3Yujia Cai4Lei Zhao5Namita Agrawal6Nikita Gonugunta7Xiaohu Wang8Liam Mccarthy9Varshitha Kasulabada10Akshita Pattnaik11Atique U. Ahmed12James Miller13Charles Kulwin14Aaron Cohen-Gadol15Troy Payner16Chih-Ta Lin17Jesse J. Savage18Brandon Lane19Kevin Shiue20Aaron Kamer21Mitesh Shah22Gopal Iyer23Gordon Watson24Christina Kendziorski25Mahua Dey26Department of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurological Surgery, Northwestern University, Chicago, IL, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USAGoodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USAGoodman Campbell Brain and Spine Neurological Surgery, Indianapolis, IN, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Clinical Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Human Oncology, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USADepartment of Biostatistics and Medical Informatics, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USADepartment of Neurosurgery, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422400823XGenomicsGenomic analysisCancer systems biologyCancer |
| spellingShingle | Jack M. Shireman Quinn White Zijian Ni Chitrasen Mohanty Yujia Cai Lei Zhao Namita Agrawal Nikita Gonugunta Xiaohu Wang Liam Mccarthy Varshitha Kasulabada Akshita Pattnaik Atique U. Ahmed James Miller Charles Kulwin Aaron Cohen-Gadol Troy Payner Chih-Ta Lin Jesse J. Savage Brandon Lane Kevin Shiue Aaron Kamer Mitesh Shah Gopal Iyer Gordon Watson Christina Kendziorski Mahua Dey Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure iScience Genomics Genomic analysis Cancer systems biology Cancer |
| title | Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| title_full | Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| title_fullStr | Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| title_full_unstemmed | Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| title_short | Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| title_sort | genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure |
| topic | Genomics Genomic analysis Cancer systems biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S258900422400823X |
| work_keys_str_mv | AT jackmshireman genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT quinnwhite genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT zijianni genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT chitrasenmohanty genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT yujiacai genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT leizhao genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT namitaagrawal genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT nikitagonugunta genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT xiaohuwang genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT liammccarthy genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT varshithakasulabada genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT akshitapattnaik genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT atiqueuahmed genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT jamesmiller genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT charleskulwin genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT aaroncohengadol genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT troypayner genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT chihtalin genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT jessejsavage genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT brandonlane genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT kevinshiue genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT aaronkamer genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT miteshshah genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT gopaliyer genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT gordonwatson genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT christinakendziorski genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure AT mahuadey genomicanalysisofhumanbrainmetastasestreatedwithstereotacticradiosurgeryrevealsuniquesignaturebasedontreatmentfailure |