Mayo Clinic Laboratory and pathology research roundup: February 8
Share this:
The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.
Featured Abstract
High-grade glioma with pleomorphic and pseudopapillary features (HPAP): a proposed type of circumscribed glioma in adults harboring frequent TP53 mutations and recurrent monosomy 13.
Tumors of the central nervous system (CNS) often display a wide morphologic spectrum that has, until recently, been the sole basis for tumor classification. The introduction of the integrated histomolecular diagnostic approach in CNS tumors has facilitated a classification system that is increasingly data-driven and with improved alignment to clinical outcome. Here, we report a previously uncharacterized glioma type (n = 31) using unsupervised clustering analysis of DNA methylation array data from approximately 14,000 CNS tumor samples. Histologic examination revealed circumscribed growth and morphologic similarities to pleomorphic xanthoastrocytoma (PXA), astroblastoma, ependymoma, polymorphous neuroepithelial tumor of the young (PLNTY), and IDH-wildtype glioblastoma (GBM). Median age (46.5 years) was significantly older than other circumscribed gliomas and younger than GBM. Dimensionality reduction with uniform manifold approximation and projection (UMAP) and hierarchical clustering confirmed a methylation signature distinct from known tumor types and methylation classes. DNA sequencing revealed recurrent mutations in TP53 (57%), RB1 (26%), NF1 (26%), and NF2 (14%). BRAF V600E mutations were detected in 3/27 sequenced cases (12%). Copy number analysis showed increased whole chromosome aneuploidy with recurrent loss of chromosome 13 (28/31 cases, 90%). CDKN2A/B deletion (2/31, 6%) and MGMT promoter methylation (1/31, 3%) were notably rare events. Most tumors showed features of a high-grade glioma, yet survival data showed significantly better overall survival compared to GBM (p < 0.0001). In summary, we describe a previously uncharacterized glioma of adults identified by a distinct DNA methylation signature and recurrent loss of chromosome 13.
Published to PubMed This Week
- Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities.
Nature Communications - Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders, and known risk factors.
Biological Psychiatry - Tracking daratumumab clearance using mass spectrometry: implications on M protein monitoring and reusing daratumumab.
Leukemia - Myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T): Mayo-Moffitt collaborative study of 158 patients.
Blood Cancer Journal - A simple additive staging system for newly diagnosed multiple myeloma.
Blood Cancer Journal - Chronic lymphocytic leukemia (CLL) with Reed-Sternberg-like cells vs classic Hodgkin lymphoma transformation of CLL: does this distinction matter.
Blood Cancer Journal - Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence, risk factors, and effect on renal allograft function.
American Journal of Transplantation - Microbiology of hip and knee periprosthetic joint infections: a database study.
Clinical Microbiology and Infection - Mast cell sarcoma: clinicopathologic and molecular analysis of 10 new cases and review of literature.
Modern Pathology - Normal ex vivo mesenchymal stem cell function combined with abnormal immune profiles sets the stage for informative cell therapy trials in idiopathic pulmonary fibrosis patients.
Stem Cell Research and Therapy
