RT Journal
A1 Shi, Meilong
A1 Teng, Chuanqi
A1 Zhang, Shan
A1 He, Xiaobo
A1 Xu, Lingyun
A1 Han, Fengxian
A1 Wen, Rongqi
A1 Yu, Ganjun
A1 Liu, Jingwen
A1 Feng, Yang
A1 Wu, Yanfeng
A1 Ren, Yan
A1 Jin, Gang
A1 Li, Jing
T1 Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma
JF Genome Research 
JO Genome Research 
YR 2026 
FD February 01 
VO 36 
IS 2 
SP 275 
OP 290 
DO 10.1101/gr.280528.125 
UL http://genome.cshlp.org/content/36/2/275.abstract 
AB Eukaryotic genomes contain numerous transposable elements (TEs), whose dysregulation threatens genome stability and may contribute to cancer. Pancreatic adenocarcinoma (PAAD) is among the deadliest cancers, marked by abundant stroma that obscures tumor-specific molecular signals, complicating bulk-tissue analyses. Here, using 71 patient-derived PAAD organoids, we show that TE activities may potentially promote tumorigenesis and provide a source of novel immunotherapeutic targets. We identify 16 new TE-derived transcripts fused with 15 known oncogenes, exhibiting potential oncogenic function and prognostic value. Notably, LTR7-PLAAT4, present in 29% of tumors, encodes a protein variant transcriptionally regulated by FOXM1 binding to the LTR7 promoter. LTR7-PLAAT4 isoform 2 is associated with increased cholesterol ester accumulation and lipid droplet formation mediated through BSCL2 coexpression, potentially fostering tumor progression. On the immunogenic front, HLA-I immunopeptidomics of AsPC-1 cells and DAC13 organoids identify over 11,000 peptides respectively. Althought mutation-derived neoantigens are rare, several peptides are originated from TE-chimeric transcripts, including four predicted by TEprof2. The peptide FLIQHLPLV, detected in 27% of organoids, exhibits robust immunogenicity, validated by T2 binding, mass spectrometry and ELISPOT assays with HLA-genotyped PBMCs. Together, these findings suggest that TE activities may contribute to PAAD progression and diversify its immunopeptidome, providing new opportunities for molecular subtyping and potential immunotherapeutic intervention.