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Abstract 486: Pathogenic drivers and their comutations in genes frequently altered in cancer

Background - aim: The as yet publicized results from Precision Oncology trials highlight the need to define parameters that may interfere with the actionability of common pathogenic drivers. One such parameter may be the presence of multiple drivers within the same tumor. Here, we investigated the p...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.486-486
Main Authors: Kotoula, Vassiliki, Fountzilas, Elena, Koliou, Georgia-Angeliki, Papadopoulou, Kyriaki, Giannoulatou, Eleni, Tikas, Ioannis, Zagouri, Flora, Christodoulou, Christos, Pentheroudakis, Georgios, Koutras, Angelos, Pectasides, Dimitrios, Fountzilas, George
Format: Article
Language:English
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Summary:Background - aim: The as yet publicized results from Precision Oncology trials highlight the need to define parameters that may interfere with the actionability of common pathogenic drivers. One such parameter may be the presence of multiple drivers within the same tumor. Here, we investigated the properties of single and coexisting pathogenic mutations in genes frequently altered and targeted across cancers. Methods: We examined informative deep sequencing data for TP53, PIK3CA, KRAS and BRCA1 from 2672 paraffin tumors that were obtained at first diagnosis (88% stage I-III; 12% stage IV) from patients with breast (n=1745), colorectal (n=524), nasopharyngeal (n=143), gastric (n=102), biliary tree (n=81), nasopharyngeal (n=143) and ovarian (n=77) cancer. Single mutation corresponds to the presence of a pathogenic mutation in only one of these genes; co-mutation, to the presence of pathogenic mutations in ≥2 genes. We examined the status of single and co-mutations compared to disease stage and patient overall survival (OS) stratified by tumor type. Results: Pathogenic mutations in any of the 4 genes were observed in 1337 (50% of all tumors) and co-mutation in 347 tumors (28% of tumors with mutations in these genes). Single mutations and co-mutations were observed in 481 (36.0%) and 322 (24.1%) tumors for TP53, respectively; in 350 (26.0%) and 198 (14.8%) for PIK3CA; in 80 (6%) and 198 (14.8%) for KRAS; and, in 51 (3.9%) and 120 (9.0%) for BRCA1. Co-mutations of BRCA1 and KRAS were more frequent than single mutations in the two genes across tumor types (p’s
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2019-486