Abstract 3697: Gastric adenocarcinoma TP53 mutations in an ethnically admixed population

Abstract

Abstract TP53 protein is one of the most important and studied human tumor suppressors. Whereas TP53 drives the malignant transformation and is the most frequently mutated gene in human cancers, the location and the type of its mutations for specific tumor types in ethnically admixed populations have not been evaluated. In this study we employed an amplicon panel to capture and to deep-sequence all the exons of TP53 in a series of 29 tumor biopsy samples derived from Brazilian individuals diagnosed with gastric adenocarcinomas (GACs), which were compared to Asian and Europeans. TP53 sequences were obtained from Brazilian samples with the Ion Torrent AmpliSeq TP53-panel and determined in the Ion PGM Torrent and Ion Proton platforms. We generated a mean of 7.25 million reads per patient, resulting in a median coverage >13,000X. All samples were covered above 6,400X. The mutations observed here were compared to those described in patients from different ethnic groups obtained from TCGA composed for 103 Asians patients (Japan, Hong-Kong, South Korea, Vietnam) and 78 cases of Europeans. The Asian and European populations showed higher prevalence of intestinal type GAC (53.7% and 61.6%, respectively) in contrast to our cohort, in which 69% of the patients had diffuse-type GACs (p<0.001). We found 13 distinct TP53 mutations in 14 cases (48.3%). From these 14, 28.5% (4 cases) occurred in intestinal-type GACs and 71.5% (10 cases) in diffuse-type. Whereas Europeans and Asian patients shared 44.3% (n = 27) of the mutations, we found 39% of our TP53 mutations to be shared between Brazilian and European tumors and the same percentage between Brazilians and Asian patients. A single missense mutation, 17:g.7577094G>A p.Arg282Trp in the DNA binding domain in exon 8, was found in all three sample groups studied, suggesting a possible role for this mutation in GAC pathogenesis. Although TP53 is the most frequently mutated gene in GACs we found no specific patterns that could explain the differences in the clinical behavior of this tumor between Asian and non-Asian patients. Further analyses are being performed trying to correlate mutations in TP53 and other genes with the different clinical outcomes observed in GACs from Asians and non-Asians, and in a setting of high genetic admixture, as observed in Brazil. Citation Format: Melissa Pool Pizzi, Helano Carioca Freitas, Maria Galli Amorim, Bruna Durães de Figueiredo Barros, Frederico Omar Gleber-Netto, Ana Flávia Mattos Costa, Maria Dirlei Begnami, Adriane Graicer Pelosof, Diana Noronha Nunes, Emmanuel Dias-Neto. Gastric adenocarcinoma TP53 mutations in an ethnically admixed population. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3697.