Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, PIK3CA, is one of the most\nfrequently mutated genes in breast cancer, and the mutation status of PIK3CA has clinical relevance related to\nresponse to therapy.\nThe aim of our study was to investigate the mutation status of PIK3CA gene and to evaluate the concordance between\nNGS and SGS for the most important hotspot regions in exon 9 and 20, to investigate additional hotspots outside of these\nexons using NGS, and to correlate the PIK3CA mutation status with the clinicopathological characteristics of the cohort.\nMethods: In the current study, next-generation sequencing (NGS) and Sanger Sequencing (SGS) was used for the\nmutational analysis of PIK3CA in 186 breast carcinomas.\nResults: Altogether, 64 tumors had PIK3CA mutations, 55 of these mutations occurred in exons 9 and 20. Out of these 55\nmutations, 52 could also be detected by Sanger sequencing resulting in a concordance of 98.4 % between the two\nsequencing methods. The three mutations missed by SGS had low variant frequencies below 10 %. Additionally,\n4.8 % of the tumors had mutations in exons 1, 4, 7, and 13 of PIK3CA that were not detected by SGS. PIK3CA\nmutation status was significantly associated with hormone receptor-positivity, HER2-negativity, tumor grade, and\nlymph node involvement. However, there was no statistically significant association between the PIK3CA mutation\nstatus and overall survival.\nConclusions: Based on our study, NGS is recommended as follows: 1) for correctly assessing the mutation status\nof PIK3CA in breast cancer, especially for cases with low tumor content, 2) for the detection of subclonal\nmutations, and 3) for simultaneous mutation detection in multiple exons.
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