Abstract B075: Evolving molecular prescreening program to identify genomic alterations in the NOTCH pathway

Introduction: Over 2 years we have adapted our VHIO molecular prescreening program (PreScr) to identify genomic alterations in tumors of patients (pt) eligible for phase 1 clinical trials (Ph1) testing NOTCH inhibitors. This retrospective study aims to assess the prevalence of NOTCH pathway alterations in tumors and how this information was used to select therapies and to develop the PreScr. Methods: From Jan/2015 to Dec/2016, 1,832 pt had formalin-fixed, paraffin-embedded tumor samples (TS) analyzed for mutations (mut) using a customized developed Amplicon-Seq panel of 61 cancer-related genes (including FBXW7 [50% exon coverage], NOTCH1 [hotspots 5% exon coverage], NOTCH4 [hotspots 3% exon coverage]) run in Illumina MiSeq; 191 (TS) for Copy Number Alterations (CNAs) using a panel of 59 genes (including NOTCH1-4) run in NanoString NCounter; and 481 (TS) for gene expression using a panel of 26 genes (including NOTCH 1-4) run in Nanostring NCounter. NOTCH1-2 gene amplifications (ampl) were validated by FISH. Results: Tumor types samples were colorectal (CRC) n=468 (25%), lung (LC) n=273 (15%), breast (BC) n=176 (10%), gynecologic (GYNC) n= 111 (6%), head and neck (HN 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B075.