Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages

Abstract

Background Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers according to the anatomy. We previously reported a prognostic relevance of tumor location in resectable PDAC. This study is aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. Methods We detected tumor genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon rank test or Fisher exact test was used for evaluating associations between clinical characteristics, mutation frequency, and survival probability between the two cohorts. Results Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs. 82.4%, p = 0.004) and SMAD4 (42.0% vs. 21.2%, p = 0.008). At early stages (I-II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs. 26.5%, p = 0.021). At late stages (III-IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs. 75.8%, p = 0.001), higher frequency of MAPK pathway mutation (100% vs. 87.8%, p = 0.040) and lower rates of druggable genomic alterations (30.8% vs. 57.6%, p = 0.030) than pancreatic head cancers. Conclusions The molecular diversity exists between pancreatic head and body/tail cancers in both tumor initiation and progression. Pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.