Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.
Leland S HuFulvio D'AngeloTaylor M WeiskittelFrancesca Pia CarusoShannon P Fortin EnsignMylan R BlomquistMatthew J FlickLujia WangChristopher P SeredukKevin Meng-LinGustavo De LeonAshley NespodzanyJavier C UrcuyoAshlyn C GonzalesLee CurtinErika M LewisKyle W SingletonTimothy DondlingerAliya AnilNatenael B SemminehTeresa Maria Rosaria NovielloReyna A PatelPanwen WangJunwen WangJennifer M EschbacherAndrea Hawkins-DaarudPamela R JacksonItamar S GrunfeldChristian ElrodGina L MazzaSam C McGeeLisa PaulsonKamala Clark-SwansonYvette Lassiter-MorrisKris A SmithPeter NakajiBernard R BendokRichard S ZimmermanChandan KrishnaDevi P PatraNaresh P PatelMark K LyonsMatthew NealKliment DonevMaciej M MrugalaAlyx B PorterScott C BeemanTodd R JensenKathleen M SchmaindaYuxiang ZhouLeslie C BaxterChristopher L PlaisierJing LiHu LiAnna LasorellaC Chad QuarlesKristin R SwansonMichele CeccarelliAntonio IavaroneNhan L TranPublished in: Nature communications (2023)
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.
Keyphrases
- magnetic resonance imaging
- single cell
- contrast enhanced
- high grade
- genome wide
- high resolution
- computed tomography
- diffusion weighted imaging
- healthcare
- poor prognosis
- rheumatoid arthritis
- newly diagnosed
- end stage renal disease
- ejection fraction
- radiation therapy
- stem cells
- health insurance
- cell therapy
- dna methylation
- fluorescence imaging
- cerebral ischemia