Genomic characterization and prognosis of pancreatic adenosquamous carcinoma

Pancreatic adenosquamous carcinoma (PASC) is a highly rare and aggressive disease with poor prognosis. The median overall survival is less than one year. Aiming to identify the genomic characterization of the PASC, we conducted a retrospective analysis of the clinical characteristics and genomic alterations in 14 patients with PASC who underwent surgery at Beijing Hospital and Peking Union Medical College Hospital from 2010 to 2021. Genomic alterations were identified using targeted panel sequencing. We developed a PASC-specific signature to aid in the prognostic stratification of these patients. Our study revealed several genetic alterations potentially contributing to the development and progression of PASC, including TP53 mutations, MYC amplification, and CDKN2A deletion. Pathway enrichment analysis indicated that STK11 mutations, high tumor mutational burden (TMB-H), APC deletion, TERT/RICTOR amplification, and chromosomal instability (CIN-H) were significantly associated with altered pathways. Additionally, we confirmed the prognostic value of our PASC-specific signature through validation in an independent cohort of pancreatic ductal adenocarcinoma patients.