Abstract / Summary
Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, and the tumour suppressor gene TP53 is among its most frequently mutated genes. Which specific TP53 mutations dominate in PDAC, and how their spectrum differs from other cancers, is not always clear from individual cohorts. Methods. We retrieved somatic TP53 mutations from nine PDAC cohorts in cBioPortal using Python, removed overlapping patients, and classified mutations into DNA-contact hotspot, conformational hotspot, other missense and truncating groups. Frequencies were reported with 95% Wilson confidence intervals. Robustness was tested by comparing MSK with non-MSK cohorts, and PDAC was compared with TCGA colorectal and lung adenocarcinoma cohorts. Results. We analysed 2,411 PDAC patients with TP53 mutations. R175H was the most frequent mutation (6.6%; 95% CI 5.7-7.7%), followed by R273H, R282W and R248Q. About 64% of mutations were missense and 33% truncating. Results were consistent between MSK and non-MSK cohorts (Spearman rho = 0.84) and after excluding non-adenocarcinoma tumours. Hotspot missense mutations were less common in PDAC (27.6%) than in colorectal cancer (38.0%) and more common than in lung adenocarcinoma (13.1%). R175H was significantly more frequent in PDAC than in lung adenocarcinoma (6.6% vs 1.0%). Conclusions. R175H is the single most frequent TP53 mutation in PDAC, and the PDAC TP53 mutation spectrum is stable across cohorts but differs from that of other cancers. This is a preprint and has not been peer reviewed. Code: https://github.com/mahbodpouria5-wq/tp53-pdac-analysis