Investigative needle core biopsies support multimodal deep-data generation in glioblastoma
Kenny Yu, Sreyashi Basu, Gerard Baquer, Ryuhjin Ahn, Jennifer Gantchev, Sonali Jindal, Michael S. Regan, Zaki Abou-Mrad, Michael C. Prabhu, Marc Williams, Alicia D. D’Souza, Seth Malinowski, Kelsey Hopland, Yuval Elhanati, Sylwia A. Stopka, Alexei Stortchevoi, Charles Couturier, Zhong He, Jingjing Sun, Yulong Chen, Alexsandra Espejo, Kin Hoe Chow, Smitha Yerrum, Pei-Lun Kao, Brittany C. Parker Kerrigan, Lisa Norberg, Douglas Nielsen, The GBM TeamLab, Jennifer Wiley, Kathryn Partridge, Vasilena Gocheva, Ugonma N. Chukwueke, Franziska Michor, Shahiba Ogilvie, Marco Mineo, Md Amin Hossain, Jordina Rincon-Torroella, Jayne Vogelzang, Kimberly Lopez Vasquez, Isaac H. Solomon, Himanshu Soni, Anna Ball, Raziye Piranlioglu, Daniel Triggs, Alexander L. Ling, Nafisa Masud, Ana Montalvo Landivar, Marla J. Polk, Dina Elharouni, Georges Ayoub, Jian Hu, Alexandra Giantini Larsen, Pratibha Sharma, Pratibha Sharma, Christopher Douville, 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, Padmanee Sharma, Viviane Tabar, Nathalie Y.R. Agar
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.