Background
Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. In this study, we aimed to identify novel fusion transcripts in esophageal adenocarcinomas.
Methods
To identify new fusion transcripts associated with esophageal adenocarcinoma, we performed targeted RNA sequencing and PCR verification in 40 esophageal adenocarcinomas (EACs) and matched non-malignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes.
Results
Five novel in-frame fusion transcripts were identified and verified in 40 EACs as well as in a validation cohort of 15 additional EACs (in total, 55 patients): FGFR2-GAB2 (2/55, or 3.6%), NPC1-MELK (2/55, or 3.6%), USP54-CAMK2G (2/55, or 3.6%), MKL1-FBLN1 (1/55, or 1.8%), and CNOT2-C12orf49 (1/55, or 1.8%). Genomic analysis indicated that NPC1-MELK arose from a complex inter-chromosomal translocation event involving chromosomes 18, 3, and 9 with three rearrangement points, consistent with chromoplexy.
Conclusions
These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC.