Journal article
NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors
Brain pathology (Zurich, Switzerland), Vol.34(6), e13256
11/2024
DOI: 10.1111/bpa.13256
PMCID: PMC11483515
PMID: 38523251
Abstract
Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days-43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (p = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2-3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an "SFT" histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5-7::ex16-17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16-17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.
Details
- Title: Subtitle
- NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors
- Creators
- Kathryn L Eschbacher - University of IowaQuynh T Tran - St. Jude Children's Research HospitalEvgeny A Moskalev - Universitätsklinikum ErlangenSarah Jenkins - Mayo ClinicKaren Fritchie - Cleveland ClinicRobert Stoehr - Universitätsklinikum ErlangenAlissa Caron - Mayo ClinicMichael J Link - Mayo ClinicPaul D Brown - Mayo ClinicAndrew Guajardo - Johns Hopkins UniversityDaniel J Brat - Northwestern UniversityAshley Wu - University of California, San FranciscoSandro Santagata - Brigham and Women's HospitalDavid N Louis - Brigham and Women's HospitalPriscilla K Brastianos - Massachusetts General HospitalAlexander B Kaplan - Massachusetts General HospitalBrian Alexander - Dana-Farber Cancer InstituteSabrina Rossi - Bambino Gesù Children's HospitalFabio Ferrarese - Ca' Foncello HospitalDavid R Raleigh - University of California, San FranciscoMinh P Nguyen - University of California, San FranciscoJohn Gross - Johns Hopkins UniversityJose Velazquez Vega - Children's Healthcare of AtlantaFausto Rodriguez - University of California, Los AngelesArie Perry - University of California, San FranciscoMaria Martinez-Lage - Massachusetts General HospitalBrent A Orr - St. Jude Children's Research HospitalFlorian Haller - Universitätsklinikum ErlangenCaterina Giannini - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Brain pathology (Zurich, Switzerland), Vol.34(6), e13256
- DOI
- 10.1111/bpa.13256
- PMID
- 38523251
- PMCID
- PMC11483515
- NLM abbreviation
- Brain Pathol
- eISSN
- 1750-3639
- Language
- English
- Electronic publication date
- 03/24/2024
- Date published
- 11/2024
- Academic Unit
- Pathology
- Record Identifier
- 9984577035702771
Metrics
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