Abstract
INTRODUCTION
The role of chromosomal rearrangement in neoplastic transformation has been well-studied in number of cancers. However, the area remains under-studied in high-grade gliomas.
METHODS
We performed RNA-seq of 272 gliomas, identifying 214 fusion transcripts. Additional review of the literature identified an additional 772 fusion transcripts in the published literature. Analysis was performed pertaining to rearrangement hot-spots and recurrent fusion transcripts.
RESULTS
>The most common form of fusion transcript arose from joining of sequences from the same chromosome (76%) rather than sequences from difference chromosomes. Frequency of fusion transcript increased with advanced tumor grade. More fusion transcripts are found in the classical subtype of glioblastoma (P = 0.012), particularly in tumors with amplification of EGFR. Fusion transcripts were most commonly mapped to chromosomes 7 and 12, suggesting these chromosomes contain hots-spots for chromosomal rearrangement. For primary glioblastomas, the most prevalent fusion transcripts involved 1) segments of the EGFR sequence fused to other segments of EGFR or to sequences derived from non-EGFR genes (5.6%) or 2) fusion between FGFR and TACC (FGFR3-TACC3 (3.8%) and FGFR1-TACC1 (0.5%)). PTPRZ1-MET fusions are unique in that they are predominantly found in secondary glioblastomas. All three classes of the encoded fusion proteins have been shown to modulate aspects of glioblastoma biology, including tumorigenesis and invasion.
CONCLUSION
While ∼50% of glioblastoma harbor fusion transcripts, the occurrence of “driver” fusion transcripts is a relative rarity (<5%). Primary and secondary glioblastomas harbor distinct forms of “driver” fusion transcripts.