RT Journal Article SR Electronic T1 Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors JF Molecular Cancer Research JO Mol Cancer Res FD American Association for Cancer Research SP 70 OP 83 DO 10.1158/1541-7786.MCR-18-0531 VO 17 IS 1 A1 Romero-Calvo, Isabel A1 Weber, Christopher R. A1 Ray, Mohana A1 Brown, Miguel A1 Kirby, Kori A1 Nandi, Rajib K. A1 Long, Tiha M. A1 Sparrow, Samantha M. A1 Ugolkov, Andrey A1 Qiang, Wenan A1 Zhang, Yilin A1 Brunetti, Tonya A1 Kindler, Hedy A1 Segal, Jeremy P. A1 Rzhetsky, Andrey A1 Mazar, Andrew P. A1 Buschmann, Mary M. A1 Weichselbaum, Ralph A1 Roggin, Kevin A1 White, Kevin P. YR 2019 UL http://mcr.aacrjournals.org/content/17/1/70.abstract AB Patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid systems show great promise for understanding the biological underpinnings of disease and advancing therapeutic precision medicine. Despite the increased use of organoids, the fidelity of molecular features, genetic heterogeneity, and drug response to the tumor of origin remain important unanswered questions limiting their utility. To address this gap in knowledge, primary tumor- and patient-derived xenograft (PDX)-derived organoids, and 2D cultures for in-depth genomic and histopathologic comparisons with the primary tumor were created. Histopathologic features and PDAC representative protein markers (e.g., claudin 4 and CA19-9) showed strong concordance. DNA- and RNA-sequencing (RNAseq) of single organoids revealed patient-specific genomic and transcriptomic consistency. Single-cell RNAseq demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. In addition, the in vivo PDX response to FOLFIRINOX and gemcitabine/abraxane treatments were examined, which was recapitulated in vitro with organoids. This study has demonstrated that organoids are potentially invaluable for precision medicine as well as preclinical drug treatment studies because they maintain distinct patient phenotypes and respond differently to drug combinations and dosage.Implications: The patient-specific molecular and histopathologic fidelity of organoids indicate that they can be used to understand the etiology of the patient's tumor and the differential response to therapies and suggests utility for predicting drug responses.This article is featured in Highlights of This Issue, p. 1