Investigative needle core biopsies support multimodal deep-data generation in glioblastoma
Abstract Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the de...
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2025-04-01
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| Online Access: | https://doi.org/10.1038/s41467-025-58452-8 |
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| author | Kenny K. H. Yu Sreyashi Basu Gerard Baquer Ryuhjin Ahn Jennifer Gantchev Sonali Jindal Michael S. Regan Zaki Abou-Mrad Michael C. Prabhu Marc J. Williams Alicia D. D’Souza Seth W. Malinowski Kelsey Hopland Yuval Elhanati Sylwia A. Stopka Alexei Stortchevoi Charles Couturier Zhong He Jingjing Sun Yulong Chen Alexsandra B. Espejo Kin Hoe Chow Smitha Yerrum Pei-Lun Kao Brittany Parker Kerrigan Lisa Norberg Douglas Nielsen The GBM TeamLab Vinay K. Puduvalli Jason Huse Rameen Beroukhim Betty Y. S. Kim Sangeeta Goswami Adrienne Boire Sarah Frisken Michael J. Cima Matthias Holdhoff Calixto-Hope G. Lucas Chetan Bettegowda Stuart S. Levine Tejus A. Bale Cameron Brennan David A. Reardon Frederick F. Lang E. Antonio Chiocca Keith L. Ligon Forest M. White Padmanee Sharma Viviane Tabar Nathalie Y. R. Agar |
| author_facet | Kenny K. H. Yu Sreyashi Basu Gerard Baquer Ryuhjin Ahn Jennifer Gantchev Sonali Jindal Michael S. Regan Zaki Abou-Mrad Michael C. Prabhu Marc J. Williams Alicia D. D’Souza Seth W. Malinowski Kelsey Hopland Yuval Elhanati Sylwia A. Stopka Alexei Stortchevoi Charles Couturier Zhong He Jingjing Sun Yulong Chen Alexsandra B. Espejo Kin Hoe Chow Smitha Yerrum Pei-Lun Kao Brittany Parker Kerrigan Lisa Norberg Douglas Nielsen The GBM TeamLab Vinay K. Puduvalli Jason Huse Rameen Beroukhim Betty Y. S. Kim Sangeeta Goswami Adrienne Boire Sarah Frisken Michael J. Cima Matthias Holdhoff Calixto-Hope G. Lucas Chetan Bettegowda Stuart S. Levine Tejus A. Bale Cameron Brennan David A. Reardon Frederick F. Lang E. Antonio Chiocca Keith L. Ligon Forest M. White Padmanee Sharma Viviane Tabar Nathalie Y. R. Agar |
| author_sort | Kenny K. H. Yu |
| collection | DOAJ |
| description | Abstract Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX) models. Multimodal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. In conclusion, investigative biopsies provide data-rich insight into disease processes and may be useful in evaluating treatment responses. |
| format | Article |
| id | doaj-art-e920fcb7603c4e6aa5e147b3741176a7 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e920fcb7603c4e6aa5e147b3741176a72025-08-20T02:11:11ZengNature PortfolioNature Communications2041-17232025-04-0116112310.1038/s41467-025-58452-8Investigative needle core biopsies support multimodal deep-data generation in glioblastomaKenny K. H. Yu0Sreyashi Basu1Gerard Baquer2Ryuhjin Ahn3Jennifer Gantchev4Sonali Jindal5Michael S. Regan6Zaki Abou-Mrad7Michael C. Prabhu8Marc J. Williams9Alicia D. D’Souza10Seth W. Malinowski11Kelsey Hopland12Yuval Elhanati13Sylwia A. Stopka14Alexei Stortchevoi15Charles Couturier16Zhong He17Jingjing Sun18Yulong Chen19Alexsandra B. Espejo20Kin Hoe Chow21Smitha Yerrum22Pei-Lun Kao23Brittany Parker Kerrigan24Lisa Norberg25Douglas Nielsen26The GBM TeamLabVinay K. Puduvalli27Jason Huse28Rameen Beroukhim29Betty Y. S. Kim30Sangeeta Goswami31Adrienne Boire32Sarah Frisken33Michael J. Cima34Matthias Holdhoff35Calixto-Hope G. Lucas36Chetan Bettegowda37Stuart S. Levine38Tejus A. Bale39Cameron Brennan40David A. Reardon41Frederick F. Lang42E. Antonio Chiocca43Keith L. Ligon44Forest M. White45Padmanee Sharma46Viviane Tabar47Nathalie Y. R. Agar48Department of Neurosurgery, Memorial Sloan Kettering Cancer CenterImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolMIT-Harvard Health Sciences and TechnologyDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, Memorial Sloan Kettering Cancer CenterDepartment of Pathology, Dana-Farber Cancer Institute, Harvard Medical SchoolDepartment of Computational Oncology, Memorial Sloan Kettering Cancer CenterMIT-Harvard Health Sciences and TechnologyDepartment of Pathology, Dana-Farber Cancer Institute, Harvard Medical SchoolDepartment of Neurosurgery, Memorial Sloan Kettering Cancer CenterDepartment of Computational Oncology, Memorial Sloan Kettering Cancer CenterDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurosurgery, The Brain Tumor Center, Division of Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Anatomic Pathology, The Brain Tumor Center, The University of Texas MD Anderson Cancer CenterDepartment of Anatomic Pathology, The Brain Tumor Center, The University of Texas MD Anderson Cancer CenterDepartment of Neuro-Oncology, The Brain Tumor Center, Division of Cancer Medicine, The University of Texas MD Anderson Cancer CenterDepartment of Anatomic Pathology, Division of Pathology-Lab Medicine Division, The University of Texas MD Anderson Cancer CenterBroad Institute of MIT and HarvardDepartment of Neurosurgery, The Brain Tumor Center, Division of Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Neurology, Memorial Sloan Kettering Cancer CenterDepartment of Radiology, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Materials Science and Engineering, Koch Institute for Integrative Cancer ResearchThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of MedicineDepartment of Pathology, Johns Hopkins University School of MedicineDepartment of Neurosurgery, Johns Hopkins University School of MedicineKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Neurosurgery, Memorial Sloan Kettering Cancer CenterDepartment of Medical Oncology, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical SchoolDepartment of Neurosurgery, The Brain Tumor Center, Division of Surgery, The University of Texas MD Anderson Cancer CenterDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Pathology, Dana-Farber Cancer Institute, Harvard Medical SchoolMIT-Harvard Health Sciences and TechnologyImmunotherapy Platform and James P. Allison Institute, The University of Texas MD Anderson Cancer CenterDepartment of Neurosurgery, Memorial Sloan Kettering Cancer CenterDepartment of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX) models. Multimodal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. In conclusion, investigative biopsies provide data-rich insight into disease processes and may be useful in evaluating treatment responses.https://doi.org/10.1038/s41467-025-58452-8 |
| spellingShingle | Kenny K. H. Yu Sreyashi Basu Gerard Baquer Ryuhjin Ahn Jennifer Gantchev Sonali Jindal Michael S. Regan Zaki Abou-Mrad Michael C. Prabhu Marc J. Williams Alicia D. D’Souza Seth W. Malinowski Kelsey Hopland Yuval Elhanati Sylwia A. Stopka Alexei Stortchevoi Charles Couturier Zhong He Jingjing Sun Yulong Chen Alexsandra B. Espejo Kin Hoe Chow Smitha Yerrum Pei-Lun Kao Brittany Parker Kerrigan Lisa Norberg Douglas Nielsen The GBM TeamLab Vinay K. Puduvalli Jason Huse Rameen Beroukhim Betty Y. S. Kim Sangeeta Goswami Adrienne Boire Sarah Frisken Michael J. Cima Matthias Holdhoff Calixto-Hope G. Lucas Chetan Bettegowda Stuart S. Levine Tejus A. Bale Cameron Brennan David A. Reardon Frederick F. Lang E. Antonio Chiocca Keith L. Ligon Forest M. White Padmanee Sharma Viviane Tabar Nathalie Y. R. Agar Investigative needle core biopsies support multimodal deep-data generation in glioblastoma Nature Communications |
| title | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| title_full | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| title_fullStr | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| title_full_unstemmed | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| title_short | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| title_sort | investigative needle core biopsies support multimodal deep data generation in glioblastoma |
| url | https://doi.org/10.1038/s41467-025-58452-8 |
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