Full-length transcriptome atlas of gallbladder cancer reveals trastuzumab resistance conferred by ERBB2 alternative splicing.

ABSTRACT: Aberrant RNA alternative splicing in cancer generates varied novel isoforms and protein variants that facilitate cancer progression. Here, we employed the advanced long-read full-length transcriptome sequencing on gallbladder normal tissues, tumors, and cell lines to establish a comprehensive full-length gallbladder transcriptomic atlas. It is of note that receptor tyrosine kinases were one of the most dynamic components with highly variable transcript, with Erb-B2 receptor tyrosine kinase 2 (ERBB2) as a prime representative. A novel transcript, designated ERBB2 i14e, was identified for encoding a novel functional protein, and its protein expression was elevated in gallbladder cancer and strongly associated with worse prognosis. With the regulation of splicing factors ESRP1/2, ERBB2 i14e w

SUBMITTER: Wang Z 

PROVIDER: S-EPMC11825701 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature