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Update in

  • Investigative needle core biopsies support multimodal deep-data generation in glioblastoma.
    Yu KKH, Basu S, Baquer G, Ahn R, Gantchev J, Jindal S, Regan MS, Abou-Mrad Z, Prabhu MC, Williams MJ, D'Souza AD, Malinowski SW, Hopland K, Elhanati Y, Stopka SA, Stortchevoi A, Couturier C, He Z, Sun J, Chen Y, Espejo AB, Chow KH, Yerrum S, Kao PL, Kerrigan BP, Norberg L, Nielsen D; GBM TeamLab; Puduvalli VK, Huse J, Beroukhim R, Kim BYS, Goswami S, Boire A, Frisken S, Cima MJ, Holdhoff M, Lucas CG, Bettegowda C, Levine SS, Bale TA, Brennan C, Reardon DA, Lang FF, Chiocca EA, Ligon KL, White FM, Sharma P, Tabar V, Agar NYR. Yu KKH, et al. Nat Commun. 2025 Apr 28;16(1):3957. doi: 10.1038/s41467-025-58452-8. Nat Commun. 2025. PMID: 40295505 Free PMC article.

Abstract

Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies - tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses ('Multi-omics") has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient's disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.

One sentence summary: Integrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma.

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