1. DNA methylation profiling demonstrates superior diagnostic classification to RNA-sequencing in a case of metastatic meningioma
- Author
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David R. Raleigh, Harish N. Vasudevan, Julieann C. Lee, Arie Perry, Stephen T. Magill, Maria R H Castro, Nancy Ann Oberheim Bush, David A. Solomon, Michael W. McDermott, and Javier Villanueva-Meyer
- Subjects
Pathology ,Gene Expression ,lcsh:RC346-429 ,Metastasis ,Meningeal Neoplasms ,Cancer ,screening and diagnosis ,DNA methylation ,medicine.diagnostic_test ,Liver Disease ,Metastatic Meningioma ,Liver Neoplasms ,RNA sequencing ,Methylation ,Middle Aged ,Detection ,Liver biopsy ,Female ,Meningioma ,Recurrent Meningioma ,4.2 Evaluation of markers and technologies ,medicine.medical_specialty ,Clinical Sciences ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Rare Diseases ,Biopsy ,Case report ,medicine ,Genetics ,otorhinolaryngologic diseases ,Humans ,neoplasms ,lcsh:Neurology. Diseases of the nervous system ,Base Sequence ,business.industry ,Gene Expression Profiling ,Human Genome ,Neurosciences ,medicine.disease ,Brain Disorders ,nervous system diseases ,Brain Cancer ,Neurology (clinical) ,Biochemistry and Cell Biology ,RNA-seq ,business ,Transcriptome ,Digestive Diseases - Abstract
Meningiomas are the most common primary intracranial tumors, but meningioma metastases are rare. Accordingly, the clinical workup, diagnostic testing, and molecular classification of metastatic meningioma is incompletely understood. Here, we present a case report of multiply recurrent meningioma complicated by liver metastasis. We discuss the patient presentation, imaging findings, and conventional histopathologic characterization of both the intracranial lesion and the metastatic focus. Further, we perform multiplatform molecular profiling, comprised of DNA methylation arrays and RNA-sequencing, of six stereotactically-guided samples from the intracranial meningioma and a single ultrasound-guided liver metastasis biopsy. Our results show that DNA methylation clusters distinguish the liver metastasis from the intracranial meningioma samples, and identify a small focus of hepatocyte contamination with the liver biopsy. Nonetheless, DNA methylation-based classification accurately identifies the liver metastasis as a meningioma with high confidence. We also find that clustering of RNA-sequencing results distinguishes the liver metastasis from the intracranial meningiomas samples, but that differential gene expression classification is confounded by hepatocyte-specific gene expression programs in the liver metastasis. In sum, this case report sheds light on the comparative biology of intracranial and metastatic meningioma. Furthermore, our results support methylation-based classification as a robust method of diagnosing metastatic lesions, underscore the broad utility of DNA methylation array profiling in diagnostic pathology, and caution against the routine use of bulk RNA-sequencing for identifying tumor signatures in heterogeneous metastatic lesions.
- Published
- 2020