Impact of rare and multiple concurrent gene fusions on diagnostic DNA methylation classifier in brain tumors Journal Article

   


Authors: Galbraith, K.; Serrano, J.; Shen, G.; Tran, I.; Slocum, C. C.; Ketchum, C.; Abdullaev, Z.; Turakulov, R.; Bale, T.; Ladanyi, M.; Sukhadia, P.; Zaidinski, M.; Mullaney, K.; DiNapoli, S.; Liechty, B. L.; Barbaro, M.; Allen, J. C.; Gardner, S. L.; Wisoff, J.; Harter, D.; Hidalgo, E. T.; Golfinos, J. G.; Orringer, D. A.; Aldape, K.; Benhamida, J.; Wrzeszczynski, K. O.; Jour, G.; Snuderl, M.
Article Title: Impact of rare and multiple concurrent gene fusions on diagnostic DNA methylation classifier in brain tumors
Abstract: 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. ©2023 American Association for Cancer Research.
Keywords: retrospective studies; genetics; brain tumor; brain neoplasms; retrospective study; dna methylation; gene fusion; oncogene proteins, fusion; humans; human; oncogene fusion protein
Journal Title: Molecular Cancer Research
Volume: 22
Issue: 1
ISSN: 1541-7786
Publisher: American Association for Cancer Research  
Date Published: 2024-01-01
Start Page: 21
End Page: 28
Language: English
DOI: 10.1158/1541-7786.Mcr-23-0627
PUBMED: 37870438
PROVIDER: scopus
PMCID: PMC10942665
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181543116&doi=10.1158%2f1541-7786.MCR-23-0627&partnerID=40&md5=a32356c6e4a45011b820ff328324135c
Notes: Article -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Marc Ladanyi
    1326 Ladanyi
  2. Michael Zaidinski
    20 Zaidinski
  3. Purvil Sukhadia
    28 Sukhadia
  4. Kerry A Mullaney
    48 Mullaney
  5. Jamal Khalil Benhamida
    80 Benhamida
  6. Tejus Bale
    122 Bale
  7. Sara DiNapoli
    23 DiNapoli
Related MSK Work