Dna Sequencing Of The Small Bowel Adenocarcinomas To Identify Targetable Erbb2 Mutations.

e15800Background: Small bowel adenocarcinoma (SBA) is a rare malignancy of the digestive tract with limited knowledge about its genetic alterations. Methods: Eighteen tumor and normal matched samples were sequenced using the whole-exome-Illumina platform. Various agnostic analysis methods were used to identify relevant somatic mutations and the results were compared with the available TCGA datasets. To test potential targetable mutations we developed eight patient-derived xenografts (PDX) and three cell lines from freshly-collected primary or metastatic SBA tissues. Two kinase-activating ErbB2 mutations (V842I and Y803H) and one wild-type (wt) ErbB2 (n = 30) PDX models were used to measure the effect of Dacomitinib (Daco) on tumor growth. ErbB2-mutant tumor-derived cell lines were tested for Daco and Lapatinib (Lapa) response in-vitro. Reverse-phase-protein-arrays (RPPA) were used to identify molecular changes. Results: Several unexpected oncogenic mechanisms were suggested by the pattern of somatic mutat...