Faculty Collaboration Database

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures. Nat Commun 2023 Sep 28;14(1):6066

Date

09/29/2023

Pubmed ID

37770427

Pubmed Central ID

PMC10539500

DOI

10.1038/s41467-023-41559-1

Scopus ID

2-s2.0-85172828207 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Author List

Hu LS, D'Angelo F, Weiskittel TM, Caruso FP, Fortin Ensign SP, Blomquist MR, Flick MJ, Wang L, Sereduk CP, Meng-Lin K, De Leon G, Nespodzany A, Urcuyo JC, Gonzales AC, Curtin L, Lewis EM, Singleton KW, Dondlinger T, Anil A, Semmineh NB, Noviello T, Patel RA, Wang P, Wang J, Eschbacher JM, Hawkins-Daarud A, Jackson PR, Grunfeld IS, Elrod C, Mazza GL, McGee SC, Paulson L, Clark-Swanson K, Lassiter-Morris Y, Smith KA, Nakaji P, Bendok BR, Zimmerman RS, Krishna C, Patra DP, Patel NP, Lyons M, Neal M, Donev K, Mrugala MM, Porter AB, Beeman SC, Jensen TR, Schmainda KM, Zhou Y, Baxter LC, Plaisier CL, Li J, Li H, Lasorella A, Quarles CC, Swanson KR, Ceccarelli M, Iavarone A, Tran NL

Author

Kathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biological Products
Brain Neoplasms
Glioma
Homozygote
Humans
Magnetic Resonance Imaging
Sequence Deletion