Very long-term survival following resection for pancreatic cancer is not explained by commonly mutated genes: results of whole-exome sequencing analysis
Menée initialement à partir d'échantillons tumoraux prélevés sur 8 patients ayant survécu plus de 10 ans après une résection d'un adénocarcinome canalaire du pancréas, puis sur une cohorte complémentaire de 27 patients, cette étude de séquençage de l'exome suggère que la présence de gènes fréquemment mutés (KRAS, TP53, SMAD4, CDKN2A, ...) ne permet pas d'expliquer la survie à très long terme de ces patients
Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTSs). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. Experimental Design: We sequenced the exomes of 8 PDACs from patients who survived ≥10 years. Based on the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. Results: KRAS mutations were identified in 33 of 35 (94%) cancers from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identified in 4 of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared to available data from PDACs unselected for survival. Comparison of clinico-pathological features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade or nodal disease did not preclude long-term survival. Conclusion: Our results suggest that in most patients somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC.