Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors.

TitleImpact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors.
Publication TypeJournal Article
Year of Publication2024
AuthorsGalbraith K, Serrano J, Shen G, Tran I, Slocum CC, Ketchum C, Abdullaev Z, Turakulov R, Bale T, Ladanyi M, Sukhadia P, Zaidinski M, Mullaney K, DiNapoli S, Liechty BL, Barbaro M, Allen JC, Gardner SL, Wisoff J, Harter D, Hidalgo ETeresa, Golfinos JG, Orringer DA, Aldape K, Benhamida J, WrzeszczyƄski KO, Jour G, Snuderl M
JournalMol Cancer Res
Date Published2024 Jan 02
KeywordsBrain Neoplasms, DNA Methylation, Gene Fusion, Humans, Oncogene Proteins, Fusion, Retrospective Studies

UNLABELLED: DNA methylation is an essential molecular assay for central nervous system (CNS) tumor diagnostics. While some fusions define specific brain tumors, others occur across many different diagnoses. We performed a retrospective analysis of 219 primary CNS tumors with whole genome DNA methylation and RNA next-generation sequencing. DNA methylation profiling results were compared with RNAseq detected gene fusions. We detected 105 rare fusions involving 31 driver genes, including 23 fusions previously not implicated in brain tumors. In addition, we identified 6 multi-fusion tumors. Rare fusions and multi-fusion events can impact the diagnostic accuracy of DNA methylation by decreasing confidence in the result, such as BRAF, RAF, or FGFR1 fusions, or result in a complete mismatch, such as NTRK, EWSR1, FGFR, and ALK fusions.

IMPLICATIONS: DNA methylation signatures need to be interpreted in the context of pathology and discordant results warrant testing for novel and rare gene fusions.

Alternate JournalMol Cancer Res
PubMed ID37870438
PubMed Central IDPMC10942665
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P30 CA016087 / CA / NCI NIH HHS / United States
R01 CA226527 / CA / NCI NIH HHS / United States
R01 NS122987 / NS / NINDS NIH HHS / United States
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