Abstract B50: Personna Onco: A multicancer panel for mutational screening in a Brazilian cohort
Authors: Freire Maíra Cristina Menezes , Pereira Michele Araújo , Cirillo Priscila Daniele Ramos , Lopes Natália Penido , Bustamante Carolina , Guedes Rafael Lucas Muniz , Zalis Mariano 
Published: May 2019

Next-generation sequencing (NGS) technology revolutionized the medical diagnosis field through concomitant analysis of multiple regions/genes and several individuals in a single experiment. This is currently allowing the transition from traditional to precision medicine, leading to a more accurate cancer diagnosis and enabling the best selection of molecular target drugs for individual treatments. In this context, the objective of this study was to survey the spectrum and prevalence of variants in solid tumor samples using Oncomine™ Focus Assay (Thermo Fisher Scientific), a multi-biomarker NGS assay for the detection of relevant alterations (hotspots, SNVs, indels, CNVs, and gene fusions) in 52 oncogenes associated with different solid tumors. Formalin-fixed, paraffin-embedded (FFPE) samples were obtained from 362 patients (186 males and 176 females) and clinical-pathologic data were obtained from pathologist/physician responsible for each patient. Genomic DNA and total RNA were extracted from all samples. Libraries were prepared and sequenced on Ion Torrent PGM sequencer. Sequencing data was analyzed using Ion Reporter software integrated with Oncomine® Knowledgebase. A total of 106 patients (29.3%) did not present any variants and only 13 patients (3.6%) showed inconclusive results due to poor DNA/RNA quality and/or quantity. These patients were excluded from further analysis. In general, 68 CNVs, 36 fusion genes, and 245 point mutations/indels were observed for the remaining patients (n=243). The most frequent tumor type observed was lung cancer (46.5%) showing EGFR (34.5%) and KRAS (31%) as the most frequently altered genes. These mutations are: KRAS G12 hotspot (22.1%: p.G12C - 8.0%, p.G12D - 7.1%, p.G12V - 4.4%, p.G12A - 1.8%, p.G12F – 0.9%), EGFR p.E746_A750del (6.2%), and EGFR p.L858R (6.2%). Other observed tumors were colon, breast, bladder, ovary, liver, uterus, brain, skin, and bone. Interestingly, this panel allowed the identification of not commonly observed variants in these tumors such as ovary adenocarcinoma PIK3CA p.M1043I, moderately differentiated colon adenocarcinoma FGFR4 amplification, lung adenocarcinoma BRAF p.G469A, and ERBB2 amplification. All these alterations were previously associated with drug response for other cancer types. This study demonstrated that a multicancer panel plays an important role for clinicians and patients, allowing the identification of multiple druggable variants with approved therapies, potentially improving patient outcomes, and increasing the chances of getting the best treatment. In addition, the generation of large-scale results of variants in tumors contributes to the description of mutations classified as nonpathogenic and that may eventually become driver mutations.

Citation Format: Maíra Cristina Menezes Freire, Michele Araújo Pereira, Priscila Daniele Ramos Cirillo, Natália Penido Lopes, Carolina Bustamante, Rafael Lucas Muniz Guedes, Mariano Zalis. Personna Onco: A multicancer panel for mutational screening in a Brazilian cohort [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B50.