TY  - JOUR
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
Y1  - 2026/02/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 275 
EP  - 290 
DO  - 10.1101/gr.280528.125 
VL  - 36 
IS  - 2 
UR  - http://genome.cshlp.org/content/36/2/275.abstract 
N2  - 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. 
ER  -