Project description:Glioblastoma, IDH wild type (GBM) is a primary brain cancer with a poor prognosis and few effective therapies. The ability to investigate the tumor and its microenvironment during treatment would greatly enhance understanding of disease response, progression and impact of therapeutics. Stereotactic needle core biopsies are routine surgical procedures performed primarily for tumor diagnosis. Use of these biopsies for investigations into tumor and microenvironmental responses to treatment is rarely performed but holds great potential to support therapeutic monitoring and understanding of tumor evolution. However, it is unclear whether needle core biopsies are sufficient for multi-omics analysis and tumor models. Here we test the depth of data generation possible from stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analyses including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance and quantify intra and inter-sample heterogeneity. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft (PDX) models in a separate patient cohort. Dataset integration across modalities highlighted spatially mapped immune cell associated metabolic pathways, revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome, and validated inferred cell-cell ligand receptor interactions. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data and PDX models, provide data rich insight into a patient’s disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.

Project description:Systematic collection of fresh tissues for research at the time of diagnostic image-guided breast biopsy has the potential to fuel a wide variety of innovative studies. Here we report the initial experience, including safety, feasibility and laboratory proof-of-principle, with the collection and analysis of research specimens obtained via breast core needle biopsy immediately following routine clinical biopsy at a single institution over a 14-month period. Study eligibility criteria consisted of patients age 18 or older who were undergoing a clinical breast needle biopsy. Patients providing informed consent underwent one or two additional core biopsies following collection of all necessary clinical specimens. In total, 395 patients were approached and 270 consented to the research study, yielding a 68.4% consent rate. Among consenting patients, 238 lesions were biopsied for research, resulting in 446 research specimens collected. No immediate complications were observed. During the same period, zero complications were reported among the non-research procedures (1622 breast biopsy procedures). Representative research core specimens showed high diagnostic concordance with clinical core biopsies. Flow cytometry demonstrated consistent recovery of hundreds to thousands of viable cells per research core. Among a group of HER2+ tumor research specimens, HER2 assessment by flow cytometry correlated highly with immunohistochemistry (IHC) staining, and in addition revealed extensive inter- and intra-tumoral variation in HER2 levels of potential clinical relevance. Suitability for single-cell transcriptomic analysis was demonstrated for a triple-negative tumor core biopsy, revealing substantial cellular diversity in the tumor immune microenvironment, including a prognostically relevant T cell subpopulation. Thus, collection of fresh tissues for research purposes at the time of diagnostic breast biopsy is safe, feasible and efficient, and may provide a high-yield mechanism to generate a rich tissue repository for a wide variety of cross-disciplinary research.

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Investigative needle core biopsies support multimodal deep-data generation in glioblastoma [BulkRNA-seq]

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