Abstract 3991: ONCOTARGET (ONCOALVO): A custom NGS panel for therapeutic decision in solid tumors refractory to conventional therapy

Autor: Andre M. Murad, Jose Claudio Casali-da-Rocha, Juliana G. Carneiro, Ana L. Godard
Rok vydání: 2019
Předmět:
Zdroj: Cancer Research. 79:3991-3991
ISSN: 1538-7445
0008-5472
Popis: Next-generation sequencing (NGS) of tumor biopsies of both solid tumors, as well as hematological malignancies, using commercially available platforms has broadly entered routine clinical practice in medical oncology. This molecular diagnostic approach is now used mainly to test for predictive biomarkers for patients with no available further standard therapies, as diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. However, the high cost of large multigenic panels and especially the sequencing of the entire tumor exome is a concern, especially in a developing country such as Brazil. Here we report the clinical application of a panel of 57 genes that we call ONCOTARGET (ONCOALVO) which is based on the Thermo Fisher Oncomine Focus Assay, an integrated, commercially available NGS assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance, but with 5 additional genes: the homologous recombination repair (HRR) genes BRCA1, BRCA2, ATM and CHEK2 that determine tumor sensitivity to inhibitors of the PARP enzyme and also KDR, which determines sensitivity to regorafenib. Twenty-five diagnostic samples of formalin-fixed, paraffin-embedded material submitted for molecular testing over a 8-month time period were analyzed so far. All patients had advanced solid tumors already refractory to conventional systemic therapy. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent S5 sequencer. Sequencing datasets were analyzed using the Ion Reporter software. From the samples of the 39 patients tested, we found 30 potential therapy target pathogenic gene aberrations in 22 (56.4%) patients: KRAS - 7 (23.3%), BRCA1 - 6 (20%), BRCA2 - 5 (16.6%), PIK3CA - 3 (10%), MAP2K1 - 2 (6.6%), BRAF-V600E - 2 (6.6%) mutations; and also one of each: ERBB2 (3.3%), mTOR (3.3%), KIT (3.3%), ALK (3.3%) mutations and one (3,3%) CCND1 amplification. In 3 (7,69%) patients there were double mutations: BRCA1 and BRCA2 in 2 cases and BRCA2 and KRAS and one case. The Oncotarget workflow enabled a turnaround of 18 frac12 days. Taken together, ONCOTARGET was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics and therapeutic decisions with a potential to become an important assay for precision oncology in Brazil. Citation Format: Andre M. Murad, Jose Claudio Casali-da-Rocha, Juliana G. Carneiro, Ana L. Godard. ONCOTARGET (ONCOALVO): A custom NGS panel for therapeutic decision in solid tumors refractory to conventional therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3991.
Databáze: OpenAIRE
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