Impact of Ethnicity on Somatic Mutation Rates of Pancreatic Adenocarcinoma

Abstract

Background/aim: Ethnicity has an effect on survival in patients with pancreatic adenocarcinoma (PDAC), which may be reflected in the rate of somatic driver mutations. The Brazilian population represents au extensive interethnic admixture and little is known about the spectrum and rates of somatic driver mutations in Brazilian PDAC cases.

Materials and methods: Direct sequencing of six genes in 23 PDAC cases was performed and the ancestry of patients was determined using a validated panel of ancestry-informative insertion/deletion DNA polymorphisms.

Results: KRAS proto-oncogene (KRAS) was the most commonly mutated gene (60%). A novel putatively pathogenic mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (c.2948T>A; p.M983K) was identified. Mutations in epidermal growth factor receptor (EGFR) (4%), PIK3CA (4%), cyclin-dependent kinase inhibitor 2A (CDKN2A) (4%) and TP53 (8%) were noted, in rates that are less frequent than those reported for other populations. Mutations of B-Raf proto-oncogene, serine/threonine kinase (BRAF) were not present. All individuals with high African ancestral component (allelic frequency, >0.45) exhibited KRAS mutations.

Conclusion: Our results highlight the importance of the effect of ethnicity on somatic mutations in Brazilian patients with PDAC.

Keywords: BRAF; CDKN2A; EGFR; KRAS; PIK3CA; Pancreatic cancer; TP53; ethnicity.

Figure 1. Close-up view of the interface of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) kinase domain,showing the exchange between the mutated residues, in beige, andnative residues, in green. The residues MET-983 and LYS-983, whichmay affect the protein conformation are shown with stick representation.

Figure 2. Analysis of the genomic ancestry of patients with pancreaticcancer of this study. EU: European; AF: African; AM: Amerindian;CTRL: control.